Skip to main content
SpringerLink
Log in

Endothelin-Converting Enzyme Inhibitors and their Effects

  • Chapter
Endothelin and Its Inhibitors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 152))

Abstract

Previous chapters in this handbook have reviewed extensively the biochemistry and pharmacology of the family of three endothelin (ET) isopeptides and their respective precursors. Pathways responsible for the synthesis of ETs have also been introduced. In this chapter, these subjects as well as the existence and cellular/tissue localization of endothelin-converting enzyme (ECE) isoforms are nevertheless reviewed briefly as they are important in understanding the development of inhibitors of the synthesis of ET isopeptides. The major focus of the present chapter remains on the design and pharmacological properties of various types of ECE inhibitors and the effectiveness of these compounds in isolated cells, organs, tissues, and in animal models of human pathophysiology. An overall view of the comparative advantages and disadvantages of the use of ET receptor antagonists vs ECE inhibitors for the inhibition of the ET-mediated effects is also presented.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Advenier C, Lagente V, Zhang Y, Naline E (1992) Contractile activity of big endothe-lin-1 on the human isolated bronchus. Br J Pharmacol 106:883–887

    PubMed  CAS  Google Scholar 

  • Ahn K, Herman SB, Fahnoe DC (1998) Soluble human endothelin-converting enzyme-1: expression, purification, and demonstration of pronounced pH sensitivity. Arch Biochem Biophys 359:258–268

    PubMed  CAS  Google Scholar 

  • Ahn K, Knapp J, Johnson GD, Fahnoe DC (1999) Inhibitor potencies and substrate preference for endothelin converting enzyme-1 are dramatically affected by pH. 6th Int Conf ETs (Montréal, QC, Canada) p 4

    Google Scholar 

  • Ahn K, Pan SM, Zientek MA, Guy PM, Sisneros AM (1996) Characterization of endothelin converting enzyme from intact cells of a permanent human endothe-lial cell line, EA,hy926. Biochem Mol Biol Int 39:573–580

    PubMed  CAS  Google Scholar 

  • Arai K, Ashikawa N, Nakakita Y, Matsumura A, Ashizawa N, Munekata M (1993) Aspergillomarasmine A and B, potent microbial inhibitors of endothelin-convert-ing enzyme. Biosci Biotech Biochem 57:1944–1945

    CAS  Google Scholar 

  • Ashizawa N, Okumura H, Kobayashi F, Aotsuka T, Asakura R, Arai K, Ashikawa N, Matsuura A (1994a) Inhibitory activities of metal chelators on endothelin-converting enzyme. II. In vivo studies. Biol Pharm Bull 17:212–216

    PubMed  CAS  Google Scholar 

  • Ashizawa N, Okumura H, Kobayashi F, Aotsuka T, Takahashi M, Asakura R, Arai K, Matsuura A (1994b) Inhibitory activities of metal chelators on endothelin-converting enzyme. I. In vitro studies. Biol Pharm Bull 17:207–211

    PubMed  CAS  Google Scholar 

  • Auguet M, Delaflotte S, Chabrier PE, Braquet P (1992) The vasoconstrictor action of big endothelin-1 is phosphoramidon-sensitive in rabbit saphenous artery, but not in saphenous vein. Eur J Pharmacol 224:101–102

    PubMed  CAS  Google Scholar 

  • Balwierczak JL, Kukkola PJ, Savage P, Jeng AY (1995) Effects of metalloprotease inhibitors on smooth muscle endothelin-converting enzyme activity. Biochem Pharmacol 49:291–296

    PubMed  CAS  Google Scholar 

  • Barton M, Shaw S, d’Uscio LV, Moreau P, Luscher TF (1997) Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: role of ETA receptors for endothelin regulation. Biochem Biophys Res Commun 238:861–865

    PubMed  CAS  Google Scholar 

  • Battistini B, Botting R (1995) Endothelins: A Quantum Leap Forward. Drug News & Perspect 8:365–391

    Google Scholar 

  • Battistini B, D’Orléans-Juste P, Sirois P (1993) Endothelins in physiopathology; circulating plasma levels and presence in other biological fluids. Lab Invest 68:600–628

    PubMed  CAS  Google Scholar 

  • Battistini B, Dussault P (1998a) The many aspects of endothelins in ischemia-reperfusion injury: emergence of a key mediator. J Invest Surg 11:297–313

    PubMed  CAS  Google Scholar 

  • Battistini B, Dussault P (1998b) Biosynthesis, distribution and metabolism of endothe-lins in the pulmonary system. Pulm Pharmacol Ther 11:79–88

    PubMed  CAS  Google Scholar 

  • Battistini B, Dussault P (1998c) Blocking of the endothelin system: the development of receptor antagonists. Pulm Pharmacol Ther 11:97–112

    PubMed  CAS  Google Scholar 

  • Battistini B, O’Donnell LJD, Warner TD, Fournier A, Farthing MJG, Vane JR (1994) Characterization of endothelin (ET) receptor subtypes in the isolated gallbladder of the guinea-pig. Br J Pharmacol 112:1244–1250

    PubMed  CAS  Google Scholar 

  • Baynash AG, Hosoda K, Giaid A, Richardson JA, Emoto N, Hammer RE, Yanagisawa M (1994) Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 79:1277–1285

    PubMed  CAS  Google Scholar 

  • Beaudoin CN, Israel-Assayag E, Dussault P, Cormier Y, Battistini B (1999) Correlation between levels of ET-1, big ET-1, NO, total and differential cell counts in the bronchoalveolar lavage fluid in patients with inflammatory lung diseases. 6th Int Conf ETs (Montréal, QC, Canada) p 49

    Google Scholar 

  • Bertenshaw SR, Rogers RS, Stern MK, Norman BH, Moore WM, Jerome GM, Branson LM, McDonald JF, McMahon EG, Palome MA (1993a) Phosphorus-containing inhibitors of endothelin-converting enzyme: effects of the electronic nature of phosphorus on inhibitor potency. J Med Chem 36:173–176

    PubMed  CAS  Google Scholar 

  • Bertenshaw SR, Talley JJ, Rogers, Carter JS, Moore WM, Branson LM, Koboldt CM (1993b) Thiol and hydroxamic acid containing inhibitors of endothelin-converting enzyme. Bioorg Med Chem Lett 3:1953–1958

    CAS  Google Scholar 

  • Bihovsky R, Levinson BL, Loewi RC, Erhardt PW, Polokoff MA (1995) Hydroxamic acids as potent inhibitors of endothelin-converting enzyme from human bronchi-olar smooth muscle. J Med Chem 38:2119–2129

    PubMed  CAS  Google Scholar 

  • Bird JE, Waldron TL, Little DK, Asaad MM, Dorso CR, DiDonato G, Norman JA (1992) The effects of novel cathepsin E inhibitors on the big endothelin pressor response in conscious rats. Biochem Biophys Res Commun 182:224–231

    PubMed  CAS  Google Scholar 

  • Bird JE, Webb ML, Wasserman AJ, Liu EC, Giancarli MR, Durham SK (1995) Comparison of a novel ETA receptor antagonist and phosphoramidon in renal ischemia. Pharmacology 50:9–23

    PubMed  CAS  Google Scholar 

  • Bloch KD, Eddy RL, Shows TB, Quetermous T (1989) cDNA cloning and chromosomal assignment of the gene encoding endothelin 3. J Biol Chem 264:18156–18161

    PubMed  CAS  Google Scholar 

  • Bloch KD, Hong CC, Eddy RL, Shows TB, Quertermous T (1991) cDNA cloning and chromosomal assignment of the endothelin 2 gene: vasoactive intestinal contractor peptide is rat endothelin 2. Genomics 10:236–242

    PubMed  CAS  Google Scholar 

  • Bond JS, Beynon RJ (1987) Proteolysis and physiological regulation. Mol Aspects Med 9:173–287

    PubMed  CAS  Google Scholar 

  • Brown CD, Barnes K, Turner AJ (1998) Anti-peptide antibodies specific to rat endothe-lin-converting enzyme-1 isoforms reveal isoform localisation and expression. FEBS Lett 424:183–187

    PubMed  CAS  Google Scholar 

  • Cailler F, Zappulla JP, Boileau G, Crine P (1999) The N-terminal segment of endothe-lin-converting enzyme (ECE)-lb contains a di-leucine motif that can redirect neprilysin to an intracellular compartment in Madin-Darby canine kidney (MDCK) cells. Biochem J 341 (Pt 1):119–126

    PubMed  CAS  Google Scholar 

  • Caner HH, Kwan AL, Arthur A, Jeng AY, Lappe RW, Kassell NF, Lee KS (1996) Systemic administration of an inhibitor of endothelin-converting enzyme for attenuation of cerebral vasospasm following experimental subarachnoid hemorrhage. J Neurosurg 85:917–922

    PubMed  CAS  Google Scholar 

  • Chackalamannil S, Chung S, Stamford AW, McKittrick BA, Wang Y, Tsai H, Cleven R, Fawzi A, Czarniecki M (1996) Highly potent and selective inhibitors of endothe-lin converting enzyme. Bioorg Med Chem Lett 6:1257–1260

    CAS  Google Scholar 

  • Claing A, Neugebauer W, Yano M, Rae GA, D’Orléans-Juste P (1995) [Phe22]-big endothelin-1[19–37]: a new and potent inhibitor of the endothelin-converting enzyme. J Cardiovasc Pharmacol 26 [Suppl 3]:S72-S74

    PubMed  CAS  Google Scholar 

  • Cushman DW, Cheung HS (1971) Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochem Pharmacol 20:1637–1648

    CAS  Google Scholar 

  • Deng Y, Jeng AY (1992) Soluble endothelin degradation enzyme activities in various rat tissues. Biochem Cell Biol 70:1385–1389

    PubMed  CAS  Google Scholar 

  • Deng Y, Savage P, Shetty SS, Martin LL, Jeng AY (1992) Identification and partial purification of a thiol endothelin-converting enzyme from porcine aortic endothe-lial cells. J Biochem (Tokyo) 111:346–351

    CAS  Google Scholar 

  • De Lombaert S, Blanchard L,Tan J, Sakane Y, Berry C, Ghai RD (1995) Non-peptidic inhibitors of neutral endopeptidase 24.11. 1. Discovery and optimization of potency. Bioorg Med Chem Lett 5:145–150

    Google Scholar 

  • De Lombaert S, Chatelain RE, Fink CA,Trapani AJ (1996) Design and pharmacology of dual angiotensin-converting-enzyme and neutral endopeptidase inhibitors. Curr Pharmaceutical Des 2:443–462

    Google Scholar 

  • De Lombaert S, Erion MD, Tan J, Blanchard L, El-Chehabi L, Ghai RD, Sakane Y, Berry C, Trapani AJ (1994a) N-Phosphonomethyl dipeptides and their phospho-nate prodrugs, a new generation of neutral endopeptidase (NEP, EC 3.4.24.11) inhibitors. J Med Chem 37:498–511

    PubMed  Google Scholar 

  • De Lombaert S, Ghai RD, Jeng AY, Trapani AJ, Webb RL (1994b) Pharmacological profile of a non-peptidic dual inhibitor of neutral endopeptidase 24.11 and endothelin-converting enzyme. Biochem Biophys Res Commun 204:407–412

    PubMed  CAS  Google Scholar 

  • De Lombaert S, Stamford LB, Blanchard L, Tan J, Hoyer D, Diefenbacher CG, Wei D, Wallace EM, Moskal MA, Savage P, Jeng AY (1997) Potent non-peptidic dual inhibitors of endothelin-converting enzyme and neutral endopeptidase 24.11. Bioorg Med Chem 7:1059–1064

    Google Scholar 

  • Deprez P, Guillaume J, Dumas J, Vevert J.-P (1996) Thiol inhibitors of endothelin-converting enzyme. Bioorg Med Chem Lett 6:2317–2322

    CAS  Google Scholar 

  • Descombes JJ, Mennecier P, Versluys D, Barou V, de Nanteuil G, Laubie M, Verbeuren TJ (1995) S 17162 is a novel selective inhibitor of big ET-1 responses in the rat. J Cardiovasc Pharmacol 26 [Suppl 3]:S61-S64

    PubMed  CAS  Google Scholar 

  • D’Orléans-Juste P, Lidbury PS, Warner TD, Vane JR (1990) Intravascular big-endothe-lin increases circulating levels of ET-1 and prostanoids in the rabbit. Biochem Pharmacol 39:R21-R22

    PubMed  Google Scholar 

  • D’Orléans-Juste P, Télémaque S, Claing A (1991) Different pharmacological profiles of big-endothelin-3 and big-endothelin-1 in vivo and in vitro. Br J Pharmacol 104:440–444

    PubMed  Google Scholar 

  • Douglas SA (1997) Clinical development of endothelin receptor antagonists. Trends Pharmacol Sci 18:408–412

    PubMed  CAS  Google Scholar 

  • Ehrenreich H, Loffler BM, Hasselblatt M, Langen H, Oldenburg J, Subkowski T, Schilling L, Siren AL (1999) Endothelin converting enzyme activity in primary rat astrocytes is modulated by endothelin B receptors. Biochem Biophys Res Commun 261:149–155

    PubMed  CAS  Google Scholar 

  • Emori T, Hirata Y, Kanno K, Ohta K, Eguchi S, Imai T, Schichiri M, Marumo F (1991) Endothelin-3 stimulates production of endothelium-derived nitric oxide via phosphoinositide breakdown. Biochem Biophys Res Commun 174:228–235

    PubMed  CAS  Google Scholar 

  • Emoto N, Yanagisawa M (1995) Endothelin-converting enzyme-2 is a membrane-bound phosphoramidon-sensitive metalloprotease with acidic pH optimum. J Biol Chem 270:15262–15268

    PubMed  CAS  Google Scholar 

  • Ferro CJ, Webb DJ (1996) The clinical potential of endothelin receptor antagonists in cardiovascular medicine. Drugs 51:12–27

    PubMed  CAS  Google Scholar 

  • Filep JG, Battistini B, Sirois P (1993) Induction by endothelin-1 of epithelium-dependent relaxation of guinea-pig trachea in vitro: role for nitric oxide. Br J Pharmacol 109:637–644

    PubMed  CAS  Google Scholar 

  • Fujita Y, Satoh C, Tsukahara Y, Miyawaki N (1997) The properties of enzyme inhibition by a novel dual inhibitor, SA6817, of neutral endopeptidase and anglotensin-converting enzyme. Jpn Pharmacol Soc p 28 (Abstract)

    Google Scholar 

  • Fukami T, Hayama T, Amano Y, Nakamura Y, Arai Y, Matsuyama K, Yano M, Ishikawa K (1994) Aminophosphonate endothelin-converting enzyme inhibitors: potency-enhancing and selectivity-improving modifications of phosphoramidon. Bioorg Med Chem Lett 4:1257–1262

    CAS  Google Scholar 

  • Fukuroda T, Fujikawa T, Ozaki S, Ishikawa K, Yano M, Nishikibe M (1994) Clearance of circulating endothelin-1 by ETB receptors in rats. Biochem Biophys Res Commun 199:1461–1465

    PubMed  CAS  Google Scholar 

  • Fukuroda T, Noguchi K, Tsuchida S, Nishikibe M, Ikemoto F, Okada K, Yano M (1990) Inhibition of biological actions of big endothelin-1 by phosphoramidon. Biochem Biophys Res Commun 172:390–395

    PubMed  CAS  Google Scholar 

  • Grover GJ, Sleph PG, Fox M, Trippodo NC (1992) Role of endothelin-1 and big endothelin-1 in modulating coronary vascular tone, contractile function and severity of ischemia in rat hearts. J Pharmacol Exp Ther 263:1074–1082

    PubMed  CAS  Google Scholar 

  • Grunstein MM, Rosenberg SM, Schramm CM, Pawlowski NA (1991) Mechanisms of action of endothelin 1 in maturing rabbit airway smooth muscle. Am J Physiol 260 (6 Pt 1):L434-L443

    Google Scholar 

  • Harrison VJ, Ziegler T, Bouzourene K, Suciu A, Silacci P, Hayoz D (1998) Endothe-lin-1 and endothelin-converting enzyme-1 gene regulation by shear stress and flow-induced pressure. J Cardiovasc Pharmacol 31 (Suppl 1):S38-S41

    PubMed  CAS  Google Scholar 

  • Hasegawa H, Hiki K, Sawamura T, Aoyama T, Okamoto Y, Miwa S, Shimohama S, Kimura J, Masaki T (1998) Purification of a novel endothelin-converting enzyme specific for big endothelin-3. FEBS Lett 428:304–308

    PubMed  CAS  Google Scholar 

  • Hemsen A, Larsen O, Lundberg JM (1991) Characteristics of endothelin A and B binding sites and their vascular effects in pig peripheral tissues. Eur J Pharmacol 208:313–322

    PubMed  CAS  Google Scholar 

  • Hirata Y, Kanno K, Watanabe TX, Kumagaye SI, Nakajima K, Kimura T, Sakakibara S, Marumo F (1990) Receptor binding and vasoconstrictor activity of big endothe-lin. Eur J Pharmacol 176:225–228

    PubMed  CAS  Google Scholar 

  • Hisaki K, Matsumura Y, Maekawa H, Fujita K, Takaoka M, Morimoto S (1994) Conversion of Big Et-1 in the rat lung: role of phosphoramidon-sensitive endothe-lin-1-converting enzyme. Am J Physiol 266:H422-H428

    PubMed  CAS  Google Scholar 

  • Hoang MV, Turner AJ (1997) Novel activity of endothelin-converting enzyme: hydrolysis of bradykinin. Biochem J 327 (Pt l):23–26

    PubMed  CAS  Google Scholar 

  • Ikeda T, Ohta H, Okada M, Kawai N, Nakao R, Spiegl PK, Kobayashi T, Maeda S, Miyauchi T, Nishikibe M (1999) Pathophysiological roles of endothelin-1 in Dahl salt-sensitive hypertension. Hypertension 34:514–519

    PubMed  CAS  Google Scholar 

  • Ikegawa R, Matsumura Y, Takaoka M, Morimoto S (1990a) Evidence for pepstatin-sensitive conversion of porcine big endothelin-1 to endothelin-1 by the endothe-lial cell extract. Biochem Biophys Res Commun 167:860–866

    PubMed  CAS  Google Scholar 

  • Ikegawa R, Matsumura Y, Tsukahara Y, Takaoka M, Morimoto S (1990b) Phospho-ramidon, a metalloproteinase inhibitor, suppresses the secretion of endothelin-1 from cultured endothelial cells by inhibiting a big endothelin-1-converting enzyme. Biochem Biophys Res Commun 171:669–675

    PubMed  CAS  Google Scholar 

  • Ikura T, Sawamura T, Shiraki T, Hosokawa H, Kido T, Hoshikawa H, Shimada K, Tanzawa K, Kobayashi S, Miwa S, Masaki T (1994) cDNA cloning and expression of bovine endothelin-converting enzyme. Biochem Biophys Res Commun 203:1417–1422

    PubMed  CAS  Google Scholar 

  • Imai T, Hirata Y, Emori T, Yanagisawa M, Masaki T, Marumo F (1992) Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells. Hypertension 19(6 Pt 2):753–757

    Google Scholar 

  • Inagaki M, Hashimoto K, Takahashi H, Takeshita K (1993) Blood endothelin concentration from umbilical cord and preterm baby: perinatal factor and cranial ultra-sonography in the cases of abnormally high concentration. No To Hattatsu 25:385–387

    PubMed  CAS  Google Scholar 

  • Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T (1989) The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 86:2863–2867

    PubMed  CAS  Google Scholar 

  • Ishikawa S, Tsukada H, Yuasa H, Fukue M, Wei S, Onizuka M, Miyauchi T, Ishikawa T, Mitsui K, Goto K, Hori M (1992) Effects of endothelin-1 and conversion of big endothelin-l in the isolated perfused rabbit lung. J Appl Physiol 72:2387–2392

    PubMed  CAS  Google Scholar 

  • Itoh Y, Kimura C, Onda H, Fujino M (1989) Canine endothelin-2: cDNA sequence for the mature peptide. Nucleic Acids Res 17:5389

    PubMed  CAS  Google Scholar 

  • Itoh Y, Yanagisawa M, Ohkubo S, Kimura C, Kosaka T, Inoue A, Ishida N, Mitsui Y,Onda H, Fujino M (1988) Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide,endothelin: identity of human and porcine endothelin. FEBS Lett 231:440–444

    PubMed  CAS  Google Scholar 

  • Jeng AY (1997) Therapeutic potential of endothelin converting enzyme inhibitors. Exp Opin Ther Patents 7:1283–1295

    CAS  Google Scholar 

  • Jeng AY, De Lombaert S (1997) Endothelin converting enzyme inhibitors. Curr Pharmaceutical Des 3:597–614

    CAS  Google Scholar 

  • Jeng AY, De Lombaert S, Bruseo CW, Savage P. Chou M, Trapani AJ (1999) Design and synthesis of a potent and selective endothelin converting enzyme inhibitor,CGS 35066. 6th Int Conf ETs (Montréal, QC, Canada) p 16

    Google Scholar 

  • Johnson GD, Stevenson T, Ahn K (1999) Hydrolysis of peptide hormones by endo-thelin-converting enzyme-1. A comparison with neprilysin. J Biol Chem 274:4053–4058

    PubMed  CAS  Google Scholar 

  • Kashiwabara T, Inagaki Y, Ohata H, Iwamatsu A, Nomizu M, Morita A, Nishikori K (1989) Putative precursors of endothelin have less vasoconstrictor activity in vitro but a potent pressor activity in vivo. FEBS Lett 247:73–76

    PubMed  CAS  Google Scholar 

  • Kaw S, Emoto N, Jeng AY, Yanagisawa M (1995) Pharmacological characterization of cloned human ECE-1 and ECE-2. 4th Int Conf ETs (London, UK) p C6

    Google Scholar 

  • Kawaguchi H, Sawa H, Yasuda H (1990) Endothelin stimulates angiotensin I to angiotensin II conversion in cultured pulmonary artery endothelial cells. J Mol Cell Cardiol 22:839–842

    PubMed  CAS  Google Scholar 

  • Keller PM, Lee CP, Fenwick AE, Atkinson ST, Elliott JD, DeWolf WE Jr (1996) Endothelin-converting enzyme: substrate specificity and inhibition by novel analogs of phosphoramidon. Biochem Biophys Res Commun 223:372–378

    PubMed  CAS  Google Scholar 

  • Kido H, Nakano A, Okishima N, Wakabayashi H, Kishi F, Nakaya Y, Yashizumi M,Tamaki T (1998) Human chymase, an enzyme forming novel bioactive 31-amino acid length endothelins. Biol Chem 379:885–891

    PubMed  CAS  Google Scholar 

  • Kimura S, Kasuya Y, Sawamura T, Shinimi O, Sugita Y, Yanagisawa M, Goto K, Masaki T (1989) Conversion of big endothelin-1 to 21-residue endothelin-1 is essential for expression of full vasoconstrictor activity: structure activity relationships of big endothelin-1. J Cardiovasc Pharmacol 5:S5-S7

    Google Scholar 

  • Kirshbom PM, Tsui SS, DiBernardo LR, Meliones JN, Schwinn DA, Ungerleider RM, Gaynor JW (1995) Blockade of endothelin-converting enzyme reduces pulmonary hypertension after cardiopulmonary bypass and circulatory arrest. Surgery 118:440–444; (discussion) 444–445

    PubMed  CAS  Google Scholar 

  • Knap AK, Soriano A, Savage P, Del Grande D, Shetty SS (1993) Identification of a novel aspartyl endothelin-converting enzyme in porcine aortic endothelial cells.Biochem Mol Biol Int 29:739–745

    PubMed  CAS  Google Scholar 

  • Kohan DE (1997) Endothelins in the normal and diseased kidney. Am J Kidney Dis 29:2–26

    PubMed  CAS  Google Scholar 

  • Korth P, Egidy G, Parnot C, LeMoullec JM, Corvol P, Pinet F (1997) Construction, expression and characterization of a soluble form of human endothelin-converting enzyme-1. FEBS Lett 417:365–370

    PubMed  CAS  Google Scholar 

  • Ksander GM, Savage P, Trapani AJ, Balwierczak JL, Jeng AY(1998) Benzofused macro-cyclic lactams as triple inhibitors of endothelin-converting enzyme, neutral endopeptidase 24.11, and angiotensin-converting enzyme. J Cardiovasc Pharmacol 31 [Suppl 1]:S71-S73

    PubMed  CAS  Google Scholar 

  • Kukkola PJ, Bilci NA, Kozak WX, Savage P, Jeng AY (1996) Optimization of retrothiorphan for inhibition of endothelin-converting enzyme. Bioorg Med Chem Lett 6:619–624

    CAS  Google Scholar 

  • Kukkola PJ, Savage P, Sakane J, Berry C, Bilci NA, Ghai RD, Jeng AY (1995) Differential structure-activity relationships of phosphoramidon analogues for inhibition of three metalloproteases: endothelin-converting enzyme, neutral endopeptidase, and angiotensin-converting enzyme. J Cardiovasc Pharmacal 26 [Suppl 3]:S65-S68

    CAS  Google Scholar 

  • Kundu GC, Wilson IB (1992) Identification of endothelin-converting enzyme in bovine lung using a new fluorogenic substrate. Life Sci 50:965–970

    PubMed  CAS  Google Scholar 

  • Kwan AL, Bavbek M, Jeng AY, Maniara W, Toyoda T, Lappe RW, Kassell NF, Lee KS (1997) Prevention and reversal of cerebral vasospasm by an endothelin-convert-ing enzyme inhibitor, CGS 26303, in an experimental model of subarachnoid hemorrhage. J Neurosurg 87:281–286

    PubMed  CAS  Google Scholar 

  • Lees WE, Kalinka S, Meech J, Capper SJ, Cook ND, Kay J (1990) Generation of human endothelin by cathepsin E. FEBS Lett 273:99–102

    PubMed  CAS  Google Scholar 

  • Liben S, Stewart DJ, De Marte J, Perreault T (1993) Ontogeny of big endothelin-1 effects in new born piglet pulmonary vasculature. Am J Physiol 265(1 Pt 2):H139-H145

    Google Scholar 

  • Lloyd J, Schmidt JB, Hunt JT, Barrish JC, Little DK, Tymiak AA (1996) Solid phase synthesis of phosphinic acid endothelin converting enzyme inhibitors. Bioorg Med Chem Lett 6:1323–1326

    CAS  Google Scholar 

  • Love MP, Haynes WG, Gray GA, Webb DJ, McMurray JJ (1996) Vasodilator effects of endothelin-converting enzyme inhibition and endothelin ETA receptor blockade in chronic heart failure patients treated with ACE inhibitors. Circ 94:2131–2137

    CAS  Google Scholar 

  • Marsden PA, Sultan P, Cybulsky M, Gimbrone MA Jr, Brenner BM, Collins T (1992) Nucleotide sequence of endothelin-1 cDNA from rabbit endothelial cells. Biochim Biophys Acta 1129:249–250

    PubMed  CAS  Google Scholar 

  • Masatsugu K, Itoh H, Chun TH, Ogawa Y, Tamura N, Yamashita J, Doi K, Inoue M, Fukunaga Y, Sawada N, Saito T, Korenaga R, Ando J, Nakao K (1998) Physiologic shear stress suppresses endothelin-converting enzyme-1 expression in vascular endothelial cells. J Cardiovasc Pharmacol 31 [Suppl 1]:S42-S45

    PubMed  CAS  Google Scholar 

  • Massa MA, Patt WC, Ahn K, Sisneros AM, Herman SB, Doherty A (1998) Synthesis of novel substituted pyridines as inhibitors of endothelin converting enzyme-1 (ECE-1). Bioorg Med Chem Lett 8:2117–2122

    PubMed  CAS  Google Scholar 

  • Matsumura Y, Fujita K, Takaoka M, Morimoto S (1993a) Big endothelin-3-induced hypertension and its inhibition by phosphoramidon in anesthetized rats. Eur J Pharmacol 230:89–93

    PubMed  CAS  Google Scholar 

  • Matsumura Y, Hisaki K, Takaoka M, Morimoto S (1990a) Phosphoramidon, a metal-loproteinase inhibitor, suppresses the hypertensive effect of big endothelin-1. Eur J Pharmacol 185:103–106

    PubMed  CAS  Google Scholar 

  • Matsumura Y, Ikegawa R, Suzuki Y, Takaoka M, Uchida T, Kido H, Shinyama H, Hayashi K, Watanabe M, Morimoto S (1991a) Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: the relationship to endothelin-1 levels in the cerebrospinal fluid. Life Sci 49:841–848

    PubMed  CAS  Google Scholar 

  • Matsumura Y, Ikegawa R, Tsukahara Y, Takaoka M, Morimoto S (1990b) Conversion of big endothelin-1 to endothelin-1 by two types of metalloproteinases derived from porcine aortic endothelial cells. FEBS Lett 272:166–170

    PubMed  CAS  Google Scholar 

  • Matsumura Y, Ikegawa R, Tsukahara Y, Takaoka M, Morimoto S (1991b) Conversion of big endothelin-1 to endothelin-1 by two-types of metalloproteinases of cultured porcine vascular smooth muscle cells. Biochem Biophys Res Commun 178:899–905

    PubMed  CAS  Google Scholar 

  • Matsumura Y, Ikegawa R, Tsukahara Y, Takaoka M, Morimoto S (1991c) N-ethylmaleimide differentiates endothelin-converting activity by two types of metalloproteinases derived from vascular endothelial cells. Biochem Biophys Res Commun 178:531–538

    PubMed  CAS  Google Scholar 

  • Matsumura Y, Tsukahara Y, Kininobu K, Takaoka M, Morimoto S (1992) Phospho-ramidon-sensitive endothelin-converting enzyme in vascular endothelial cells converts big endothelin-1 and big endothelin-3 to their mature form. FEBS Lett 305:86–90

    PubMed  CAS  Google Scholar 

  • Matsumura Y, Okumura H, Asakura R, Ashizawa N, Takahashi M, Kobayashi F, Ashikawa N, Arai K (1993b) Pharmacological profiles of aspergillomarasmines as endothelin-converting enzyme inhibitors. Jpn J Pharmacol 63:187–193

    Google Scholar 

  • Matsuura A, Okumura H, Ashizawa N, Kobayashi F (1992) Big endothelin-1-induced sudden death is inhibited by phosphoramidon in mice. Life Sci 50:1631–1638

    PubMed  CAS  Google Scholar 

  • McKay KO, Armour CL, Black JL (1996) Endothelin receptors and activity differ in human, dog, and rabbit lung. Am J Physiol 270(1 Pt 1):L37-L43

    Google Scholar 

  • McKay KO, Battistini B, Jeng AY, Sirois P, Black JL (1997) Endothelin-converting enzyme activity in human airways. ALA/ATS Int Conf (San Francisco, CA, USA) p 8 (Abstract)

    Google Scholar 

  • McKittrick BA, Czarniecki MF, Charckalamannil S, Chung S, Defrees S, Stamford AW (1996a) Phosphinic acid derivatives. Intern Patent Appl WO9600732A1

    Google Scholar 

  • McKittrick BA, Stamford AW, Weng X, Ma K, Chackalamannil S, Czarniecki M, Cleven RM, Fawzi AB (1996b) Design and synthesis of phosphinic acids that triply inhibit endothelin converting enzyme, angiotensin converting enzyme and neutral endopeptidase 24.11. Bioorg Med Chem Lett 6:1629–1634

    Google Scholar 

  • McMahon EG, Fok KF, Moore WM, Smith CE, Siegel NR, Trapani AJ (1989) In vitro and in vivo activity of chymotrypsin-activated big endothelin (porcine 1–40). Biochem Biophys Res Commun 161:406–413

    PubMed  CAS  Google Scholar 

  • McMahon EG, Palomo MA, Brown MA, Bertenshaw SR, Carter JS (1993) Effect of phosphoramidon (endothelin converting enzyme inhibitor) and BQ-123 (endothe-lin receptor subtype A antagonist) on blood pressure in hypertensive rats. Am J Hypertens 6:667–673

    PubMed  CAS  Google Scholar 

  • McMahon EG, Palomo MA, Moore WM (1991a) Phosphoramidon blocks the pressor activity of big endothelin(l-39) and lowers blood pressure in spontaneously hypertensive rats. J Cardiovasc Pharmacol 17 [Suppl 7]:S29-S33

    PubMed  CAS  Google Scholar 

  • McMahon EG, Palomo MA, Moore WM, McDonald JF, Stern MK (1991b) Phospho-ramidon blocks the pressor activity of porcine big endothelin-l-(l-39) in vivo and conversion of big endothelin-l-(l-39) to endothelin-l-(l-21) in vitro. Proc Natl Acad Sci USA 88:703–707

    PubMed  CAS  Google Scholar 

  • Meil J et al. (1998) Naunyn-Schmiedeberg’s Arch Pharmacol 358 (Suppl 1):R514

    Google Scholar 

  • Minamino T, Kurihara H, Takahashi M, Shimada K, Maemura K, Oda H, Ishikawa T, Uchiyama T, Tanzawa K, Yazaki Y (1997) Endothelin-converting enzyme expression in the rat vascular injury model and human coronary atherosclerosis. Circulation 95:221–230

    PubMed  CAS  Google Scholar 

  • Morita A, Nomizu M, Okitsu M, Horie K, Yokogoshi H, Roller PP (1994) D-Val22 containing human big endothelin-1 analog, [D-Val22] big ET-1[16–38], inhibits the endothelin converting enzyme. FEBS Lett 353:84–88

    PubMed  CAS  Google Scholar 

  • Nakahara S, Emoto N, Matsuo M (1999) Isolation of an alternative spliced variant of bovine ECE-2. 6th Int Conf ETs (Montréal, QC, Canada) ET-6 abstract book p 3

    Google Scholar 

  • Nakano A, Kishi F, Minami K, Wakabayashi H, Nakaya Y, Kido H (1997) Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acid-length endothelins by chymase from human mast cells. J Immunol 159:1987–1992

    PubMed  CAS  Google Scholar 

  • Naomi S, Iwaoka T, Disashi T, Inoue J, Kanesaka Y, Tokunaga H, Tomita K (1998) Endothelin-1 inhibits endothelin-converting enzyme-1 expression in cultured rat pulmonary endothelial cells. Circulation 97:234–236

    PubMed  CAS  Google Scholar 

  • Nichols JS, Berman J, Wypij DM, Wiseman JS (1991) Evidence against a role for aspartyl proteases in intracellular processing of big endothelin. J Cardiovasc Pharmacol 17 [Suppl 7]:S10-S12

    PubMed  CAS  Google Scholar 

  • Nishikori K, Akiyama H, Inagaki Y, Ohta H, Kashiwabara T, Iwamutsu A, Nomizu M, Morita A (1991) Receptor binding affinity and biological activity of C-terminal elongated forms of endothelin-1. Neurochem Int 18:535–539

    PubMed  CAS  Google Scholar 

  • Noguchi K, Fukuroda T, Ikeno Y, Hirose H, Tsukada Y, Nishikibe M, Ikemoto F, Matsuyama K, Yano M (1991) Local formation and degradation of endothelin-1 in guinea-pig airway tissues. Biochem Biophys Res Commun 179:830–835

    PubMed  CAS  Google Scholar 

  • Norcini G, Santangelo F (1995) N-Heteroaryl substituted derivatives of propanamide useful in the treatment of cardiovascular diseases. EP0636630A1

    Google Scholar 

  • Nunez DJ, Taylor EA, Oh VM, Schofield JP, Brown MJ (1991) Endothelin-1 mRNA expression in the rat kidney. Biochem J 275 (Pt 3):817–819

    PubMed  CAS  Google Scholar 

  • Ohkubo S, Ogi K, Hosoya M, Matsumoto H, Suzuki N, Kimura C, Ondo H, Fujino M (1990) Specific expression of human endothelin-2 (ET-2) gene in a renal adeno-carcinoma cell line. Molecular cloning of cDNA encoding the precursor of ET-2 and its characterization. FEBS Lett 274:136–140

    PubMed  CAS  Google Scholar 

  • Ohnaka K, Takayanagi R, Nishikawa M, Haji M, Nawata H (1993) Purification and characterization of a phosphoramidon-sensitive endothelin-converting enzyme in porcine aortic endothelium. J Biol Chem 268:26759–26766

    PubMed  CAS  Google Scholar 

  • Ohnaka K, Takayanagi R, Yamauchi T, Okazaki H, Ohashi M, Umeda F, Nawata H (1990) Identification and characterization of endothelin-converting activity in cultured bovine endothelial cells. Biochem Biophys Res Commun 168:1128–1136

    PubMed  CAS  Google Scholar 

  • Ohnaka K, Takayanagi R, Yamauchi T, Umeda F, Nawata H (1991) Cultured bovine endothelial cells convert big endothelin isopeptides to mature endothelin isopep-tides. Biochem Int 23:499–506

    PubMed  CAS  Google Scholar 

  • Okada K, Miyazaki Y, Takada J, Matsuyama K, Yamaki T, Yano M (1990) Conversion of big endothelin-1 by membrane-bound metalloendopeptidase in cultured bovine endothelial cells. Biochem Biophys Res Commun 171:1192–1198

    PubMed  CAS  Google Scholar 

  • Okada K, Takada J, Arai Y, Matsuyama K, Yano M (1991) Importance of the C-termi-nal region of big endothelin-1 for specific conversion by phophoramidon-sensitive endothelin-converting enzyme. Biochem Biophys Res Commun 180:1019–1023

    PubMed  CAS  Google Scholar 

  • Onda H, Ohkubo S, Kosaka T, Yasuhara T, Ogi K, Hosoya M, Matsumoto H, Suzuki N, Kitada C, Ishibashi Y (1991) Expression of endothelin-2 (ET-2) gene in a human renal adenocarcinoma cell line: purification and cDNA cloning of ET-2. J Cardio-vasc Pharmacol 17 [Suppl 7]:S39-S43

    CAS  Google Scholar 

  • Onda H, Ohkubo S, Ogi K, Kosaka T, Kimura C, Matsumoto H, Suzuki N, Fujino M (1990) One of the endothelin gene family, endothelin 3 gene, is expressed in the placenta. FEBS Lett 261:327–330

    PubMed  CAS  Google Scholar 

  • Opgenorth TJ, Wu-Wong JR, Shiosaki K (1992) Endothelin-converting enzymes. FASEB J 6:2653–2659

    PubMed  CAS  Google Scholar 

  • Patel TR (1996) Therapeutic potential of endothelin receptor antagonists in cere-brovascular disease CNS. Drugs 5:293–310

    CAS  Google Scholar 

  • Patil AD, Freyer AJ, Breen A, Carte B, Johnson RK (1996) Halistanol disulfate B, a novel sulfated sterol from the sponge Pachastrella sp.: inhibitor of endothelin converting enzyme. J Nat Prod 59:606–608

    PubMed  CAS  Google Scholar 

  • Patil AD, Freyer AJ, Eggleston DS, Haltiwanger RC, Tomcowicz B, Breen A, Johnson RK (1997) Daleformis, a new phytoalexin from the roots of Dalea filiciformis: an inhibitor of endothelin converting enzyme. J Nat Prod 60:306–308

    PubMed  CAS  Google Scholar 

  • Pelletier S, Battistini B, Jeng AY, Sirois P (1998) Effects of dual endothelin-converting enzyme/neutral endopeptidase inhibitors, CGS 26303 and CGS 26393, on lipo-polysaccharide or interleukin-1 beta-stimulated release of endothelin from guinea pig tracheal epithelial cells. J Cardiovasc Pharmacol 31 [Suppl 1]:S10-S12

    PubMed  CAS  Google Scholar 

  • Pham D, Battistini B, Gravel M-J, Nolet A, Jeng AY, Sirois P, Escher E (1998) Protective effects of ECE/NEP inhibitors in neointimal formation after rat carotid balloon angioplasty. FASEB J 12:A402

    Google Scholar 

  • Plumpton C, Kalinka S, Martin RC, Horton JK, Davenport AP (1994) Effects of phosphoramidon and pepstatin A on the secretion of endothelin-1 and big endothelin-1 by human umbilical vein endothelial cells: measurement by two-site enzyme-linked immunosorbent assays. Clin Sci (Colch) 87:245–251

    CAS  Google Scholar 

  • Pollock DM, Divish BJ, Milicic I, Novostad EI, Burres NS, Opgenorth TJ (1993) In vivo characterization of a phosphoramidon-sensitive endothelin-converting enzyme in the rat. Eur J Pharmacol 231:459–464

    PubMed  CAS  Google Scholar 

  • Pons F,Touvay C, Lagente V, Mencia-Huerta JM, Braquet P (1991) Bronchopulmonary and pressor effects of big-endothelin-1 in the guinea-pig. Neurochem Int 18:481483

    Google Scholar 

  • Rae GA, Calixto JB, D’Orléans-Juste P (1993a) Big-endothelin-1 contracts rat isolated uterus via a phosphoramidon-sensitive endothelin ETA receptor-mediated mechanism. Eur J Pharmacol 240:113–119

    PubMed  CAS  Google Scholar 

  • Rae GA, Calixto JB, D’Orléans-Juste P (1993b) Conversion of big endothelin-1 in rat uterus causes contraction mediated by ETA receptors. J Cardiovasc Pharmacol 22:S192-S195

    PubMed  CAS  Google Scholar 

  • Russell FD, Davenport AP (1999) Evidence for intracellular endothelin-converting enzyme-2 expression in cultured human vascular endothelial cells. Circ Res 84:891–896

    PubMed  CAS  Google Scholar 

  • Russell FD, Skepper JN, Davenport AP (1998) Evidence using immunoelectron microscopy for regulated and constitutive pathways in the transport and release of endothelin. J Cardiovasc Pharmacol 31:424–430

    PubMed  CAS  Google Scholar 

  • Russo DCW, Redman CM, Lee S (1999) The Kell blood group protein, that preferentially processes big endothelin-3, is widely expressed. 6th Int Conf ETs (Montréal, QC, Canada) ET-6 abstract book p 3

    Google Scholar 

  • Saida K, Mitsui Y (1991) Structure of the precursor for vasoactive instestinal contractor (VIC): its comparison with those of endothelin-1 and endothelin-3. J Cardio-vasc Pharmacol 17 [Suppl 7]:S55-S58

    CAS  Google Scholar 

  • Saida K, Mitsui Y, Ishida N (1989) A novel peptide, vasoactive intestinal contractor, of a new (endothelin) peptide family. Molecular cloning, expression, and biological activity. J Biol Chem 264:14613–14616

    PubMed  CAS  Google Scholar 

  • Sakurai T, Yanagisawa M, Inoue A, Ryan US, Kimura S, Mitsui Y, Goto K, Masaki T (1991) cDNA cloning, sequence analysis and tissue distribution of rat preproen-dothelin-1 mRNA. Biochem Biophys Res Commun 175:44–47

    PubMed  CAS  Google Scholar 

  • Sakurai T, Yanagisawa M, Masaki T (1992) Molecular characterization of endothelin receptors. Trends Pharmacol Sci 13:103–108

    PubMed  CAS  Google Scholar 

  • Sansom CE, Hoang VM, Turner AJ (1995) Molecular modeling of the active site of endothelin-converting enzyme. J Cardiovasc Pharmacol 26 [Suppl 3]:S75-S77

    PubMed  CAS  Google Scholar 

  • Sato R, Iijima Y, Matsushita H, Negishi A, Takamatsu Y, Haruyama H, Kinoshita T, Kodama K, Ishii A (1996) Compound B90063. Jpn Patent JP8208646A

    Google Scholar 

  • Savage P, De Lombaert S, Shimada K, Tanzawa K, Jeng AY (1998) Differential inhibition of wild-type endothelin-converting enzyme-1 and its mutants. J Cardiovasc Pharmacol 31 [Suppl 1]:S16-S18

    PubMed  CAS  Google Scholar 

  • Savage P, Shetty SS, Martin LL, Jeng AY (1993) Conversion of proendothelin-1 into endothelin-1 by aspartylproteases. Int J Peptide Protein Res 42:227–232

    CAS  Google Scholar 

  • Sawamura T, Kasuya Y, Matsushita Y, Suzuki N, Shinmi O, Kishi N, Sugita Y, Yanagi-sawa M, Goto K, Masaki T, Kimura S (1991) Phosphoramidon inhibits the intra-cellular conversion of big endothelin-1 to endothelin-1 in cultured endothelial cells. Biochem Biophys Res Commun 174:779–784

    PubMed  CAS  Google Scholar 

  • Sawamura T, Kimura S, Shinmi O, Sugita Y, Kobayashi M, Mitsui Y, Yanagisawa M, Goto K, Masaki T (1990a) Characterization of endothelin-converting enzyme activities in soluble fraction of bovine cultured endothelial cells. Biochem Biophys Res Commun 169:1138–1144

    PubMed  CAS  Google Scholar 

  • Sawamura T, Kimura S, Shinmi O, Sugita Y, Yanagisawa M, Goto K, Masaki T (1990b) Purification and characterization of putative endothelin converting enzyme in bovine adrenal medulla: evidence for a cathepsin D-like enzyme. Biochem Biophys Res Commun 168:1230–1236

    PubMed  CAS  Google Scholar 

  • Sawamura T, Shinmi O, Kishi N, Sugita Y, Yanagisawa M, Goto K, Masaki T, Kimura S (1990c) Analysis of big endothelin-1 digestion by cathepsin D. Biochem Biophys Res Commun 172:883–889

    PubMed  CAS  Google Scholar 

  • Sawamura T, Shinmi O, Kishi N, Sugita Y, Yanagisawa M, Goto K, Masaki T, Kimura S (1993) Characterization of phosphoramidon-sensitive metalloproteinases with endothelin-converting enzyme activity in porcine lung membrane. Biochem Biophys Acta 1161:295–302

    PubMed  CAS  Google Scholar 

  • Schmidt M, Krörger B,Jacob E, Seulberger H, Subkowski T, Otter R, Meyer T, Schmalz-ing G, Hillen H (1994) Molecular characterization of human and bovine endothe-lin-converting enzyme (ECE-1). FEBS Lett 356:238–243

    PubMed  CAS  Google Scholar 

  • Schultz SC, Grady B, Cole F, Hamilton I, Burhop K, Malcom DS (1993) A role for endothelin and nitric oxide in the pressor response to diaspirin cross-linked hemoglobin. J Lab Clin Med 122:301–308

    PubMed  CAS  Google Scholar 

  • Schweizer A, Valdenaire O, Koster A, Lang Y, Schmitt G, Lenz B, Bluethmann H, Rohrer J (1999) Neonatal lethality in mice deficient in XCE, a novel member of the endothelin-converting enzyme and neutral endopeptidase family. J Biol Chem 274:20450–20456

    PubMed  CAS  Google Scholar 

  • Schweizer A, Valdenaire O, Nelbock P, Deuschle U, Dumas M, Edwards JB, Stumpf JG, Loffler BM (1997) Human endothelin-converting enzyme (ECE-1): three isoforms with distinct subcellular localizations. Biochem J 328:871–877

    PubMed  CAS  Google Scholar 

  • Seymour AA, Abboa-Offei B, Asaad MM, Rogers WL (1991) Evaluation of SQ 28,603, an inhibitor of neutral endopeptidase, in conscious monkeys. Can J Physiol Pharmacol 69:1609–1617

    PubMed  CAS  Google Scholar 

  • Shetty SS, Savage P, DelGrande D, De Lombaert S, Jeng AY (1998) Characterization of CGS 31447, a potent and nonpeptidic endothelin-converting enzyme inhibitor. J Cardiovasc Pharmacol 31 [Suppl 1]:S68-S70

    PubMed  CAS  Google Scholar 

  • Shiba R, Sakurai T, Yamada G, Morimoto H, Saito A, Masaki T, Goto K (1992) Cloning and expression of rat preproendothelin-3 cDNA. Biochem Biophys Res Commun 186:588–594

    PubMed  CAS  Google Scholar 

  • Shields PP, Gonzales TA, Charles D, Gilligan JP, Stern W (1991) Accumulation of pepstatin in cultured endothelial cells and its effects on endothelin processing. Biochem Biophys Res Commun 177:1006–1012

    PubMed  CAS  Google Scholar 

  • Shimada K, Matsushita Y, Wakabayashi K, Takahashi M, Matsubara A, Iijima Y, Tanzawa K (1995) Cloning and functional expression of human endothelin-converting enzyme cDNA. Biochem Biophys Res Commun 207:807–812

    PubMed  CAS  Google Scholar 

  • Shimada K, Takahashi M, Tanzawa K (1994) Cloning and functional expression of endothelin-converting enzyme from rat endothelial cells. J Biol Chem 269: 18275–18278

    PubMed  CAS  Google Scholar 

  • Shimada K, Takahashi M, Turner AJ, Tanzawa K (1996) Rat endothelin-converting enzyme-1 forms a dimer through Cys412 with a similar catalytic mechanism and a distinct substrate binding mechanism compared with neutral endopeptidase-24.11. Biochem J 315:863–867

    PubMed  CAS  Google Scholar 

  • Shiosaki K, Tasker AS, Sullivan GM, Sorensen BK, von Geldern TW, Wu-Wong JR, Marselle CA, Opgenorth TJ (1993) Potent and selective inhibitors of an aspartyl protease-like endothelin-converting enzyme identified in rat lung. J Med Chem 36:468–478

    PubMed  CAS  Google Scholar 

  • Suzuki N, Matsumoto H, Miyauchi T, Kitada C, Tsuda M, Goto K, Masaki T, Fujino M (1991) Sandwich-enzyme immunoassays for endothelin family peptides. J Cardiovasc Pharmacol 17 [Suppl 7]:S420-S422

    PubMed  CAS  Google Scholar 

  • Takada J, Okada K, Ikenaga T, Matsuyama K, Yano M (1991) Phosphoramidonsensitive endothelin-converting enzyme in the cytosol of cultured bovine endothelial cells. Biochem Biophys Res Commun 176:860–865

    PubMed  CAS  Google Scholar 

  • Takahashi M, Matsushita Y, Iijima Y, Tanzawa K (1993) Purification and characterization of endothelin-converting enzyme from rat lung. J Biol Chem 268:21394–21398

    PubMed  CAS  Google Scholar 

  • Takahashi T, Kanda T, Inoue M, Sumino H, Kobayashi I, Iwamoto A, Nagai R (1998) Endothelin Converting enzyme inhibitor protects development of right ventricular overload and medial thickening of pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension. Life Sci 63:PL137-PL143

    PubMed  CAS  Google Scholar 

  • Takai S, Shiota N, Jin D, Miyazaki M (1998) Chymase processes big-endothelin-2 to endothelin-2-(l-31) that induces contractile responses in the isolated monkey trachea. Eur J Pharmacol 358:229–233

    PubMed  CAS  Google Scholar 

  • Takaishi S, Tuchiya N, Sato A, Negishi T, Takamatsu Y, Matsushita Y, Watanabe T, Iijima Y, Haruyama H, Kinoshita T, Tanaka M, Kodama K (1998) B-90063, a novel endothelin converting enzyme inhibitor isolated from a new marine bacterium, Blastobacter sp. SANK 71894. J Antibiot (Tokyo) 51:805–815

    CAS  Google Scholar 

  • Takaoka M, Hukumori Y, Shiragami K, Ikegawa R, Matsumura Y, Morimoto S (1990a) Proteolytic processing of porcine big endothelin-1 catalyzed by cathepsin D. Biochem Biophys Res Commun 173:1218–1223

    PubMed  CAS  Google Scholar 

  • Takaoka M, Miyata Y, Takenobu Y, Ikegawa R, Matsumura Y, Morimoto S (1990b) Mode of cleavage of pig big endothelin-1 by chymotrypsin. Production and degradation of mature endothelin-1. Biochem J 270:541–544

    PubMed  CAS  Google Scholar 

  • Takaoka M, Takenobu Y, Miyata Y, Ikegawa R, Matsumura Y, Morimoto S (1990c) Pepsin, an aspartic protease, converts porcine big endothelin to 21-residue endothelin. Biochem Biophys Res Commun 166:436–442

    PubMed  CAS  Google Scholar 

  • Télémaque S, D’Orléans-Juste P (1991) Presence of a phosphoramidon-sensitive endothelin-converting enzyme which converts big-endothelin-1, but not big-endothelin-3, in the rat vas deferens. Naunyn-Schmiedeberg’s Arch Pharmacol 344:505–507

    Google Scholar 

  • Trapani AJ, Balwierczak JL, Lappe RW, Stanton JL, Graybill SC, Hopkins MF, Savage P, Sperbeck DM, Jeng AY (1993) Effects of metalloprotease inhibitors on the conversion of proendothelin-1 to endothelin-1. Biochem Mol Biol Int 31:861–867

    PubMed  CAS  Google Scholar 

  • Trapani AJ, De Lombaert SD, Kuzmich S, Jeng AY (1995) Inhibition of big ET-1-induced pressor response by an orally active dual inhibitor of endothelin-converting enzyme and neutral endopeptidase 24.11. J Cardiovasc Pharmacol 26: S69-S71

    PubMed  CAS  Google Scholar 

  • Tsurumi Y, Fujie K, Nishikawa M, Kiyoto S, Okuhara M (1995a) Biological and pharmacological properties of highly selective new endothelin converting enzyme inhibitor WS79089B isolated from Streptosporangium roseum No. 79089. J Antibiot (Tokyo) 48:169–174

    CAS  Google Scholar 

  • Tsurumi Y, Ohhata N, Iwamoto T, Shigematsu N, Sakamoto K, Nishikawa M, Kiyoto S, Okuhara M (1994) WS79089A, B and C, new endothelin-converting enzyme inhibitors isolated from Streptosporangium roseum. NO. 79089. J Antibiot (Tokyo) 47:619–630

    CAS  Google Scholar 

  • Tsurumi Y, Ueda H, Hayashi K,Takase S, Nishikawa M, Kiyoto S, Okuhara M (1995b) WS75624 A and B, new endothelin converting enzyme inhibitors isolated from Saccharothrix sp. No. 75624. I. Taxonomy, fermentation, isolation, physicochemical preoperties and biological activities. J Antibiot (Tokyo) 48:1066–1072

    CAS  Google Scholar 

  • Turner AJ, Murphy LJ (1996) Molecular pharmacology of endothelin-converting enzymes. Biochem Pharmacol 51:91–102

    PubMed  CAS  Google Scholar 

  • Turner AJ, Tanzawa K (1997) Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX. FASEB J 11:355–364

    PubMed  CAS  Google Scholar 

  • Uchida Y, Ninomiya H, Saotome M, Nomura A, Ohtsuka M, Yanagisawa M, Goto K, Masaki T, Hasegawa S (1988) Endothelin, a novel vasoconstrictor peptide, as potent bronchoconstrictor. Eur J Pharmacol 154:227–228

    PubMed  CAS  Google Scholar 

  • Ueki A, Rosen L, Andbjer B, Agnati LF, Hallstrom A, Goiny M, Tanganelli S, Ungerstedt U, Fuxe K (1993) Evidence for a preventive action of the vigilance-promoting drug modafinil against striatal ischemic injury induced by endothelin-1 in the rat. Exp Brain Res 96:89–99

    PubMed  CAS  Google Scholar 

  • Valdenaire O, Lepailleur-Enouf D, Egidy G,Thouard A, Barret A, Vranchkx R,Tougard C, Michel JB (1999) A fourth isoform of endothelin-converting enzyme (ECE-1) is generated from an additional promoter molecular cloning and characterization. Eur J Biochem 264:341–349

    PubMed  CAS  Google Scholar 

  • Valdenaire O, Rohrbacher E, Mattei MG (1995) Organization of the gene encoding the human endothelin-converting enzyme (ECE-1). J Biol Chem 270:29794–29798

    PubMed  CAS  Google Scholar 

  • Vemulapalli S et al. (1997) Cardiovasc Drug Rev 15:260–272

    CAS  Google Scholar 

  • Vemulapalli S, Chiu PJ, Chintala M, Bernardino V (1993a) Attenuation of ischemic acute renal failure by phosphoramidon in rats. Pharmacology 47:188–193

    PubMed  CAS  Google Scholar 

  • Vemulapalli S, Watkins RW, Brown A, Cook J, Bernardino V, Chiu PJ (1993b) Disparate effects of phosphoramidon on blood pressure in SHR and DOCA-salt hypertensive rats. Life Sci 53:783–793

    PubMed  CAS  Google Scholar 

  • Wada A, Tsutamoto T, Ohnishi M, Sawaki M, Fukai D, Maeda Y, Kinoshita M (1999) Effects of a specific endothelin-converting enzyme inhibitor on cardiac, renal, and neurohumoral functions in congestive heart failure: comparison of effects with those of endothelin A receptor antagonism. Circulation 99:570–577

    PubMed  CAS  Google Scholar 

  • Wakimasu M, Mori M, Kawada A (1992) Phosphonic acid derivatives, production and use thereof. Eur Patent Appl EP 0518299A2

    Google Scholar 

  • Wallace EM, Moliterni JA, Moskal MA, Neubert AD, Marcopulos N, Stamford LB, Trapani AJ, Savage P, Chou M, Jeng AY (1998) Design and synthesis of potent, selective inhibitors of endothelin-converting enzyme. J Med Chem 41:15131523

    Google Scholar 

  • Webb ML, Bird JE, Liu EC, Rose PM, Serafino R, Stein PD, Moreland S (1995) BMS182874 is a selective, nonpeptide endothelin ETA receptor antagonist. J Pharmacol Exp Ther 272:1124–1134

    PubMed  CAS  Google Scholar 

  • Webb ML, Meek TD (1997) Inhibitors of endothelin. Med Res Rev 17:17–67

    PubMed  CAS  Google Scholar 

  • Weber C, Schmitt R, Birnboeck H, Hopfgartner G, van Marie SP, Peeters PA, Jonkman JH, Jones CR (1996) Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects. Clin Pharmacol Ther 60:124–137

    PubMed  CAS  Google Scholar 

  • Woods M, Bishop-Bailey D, Pepper JR, Evans TW, Mitchell JA, Warner TD (1998) Cytokine and lipopolysaccharide stimulation of endothelin-1 release from human internal mammary artery and saphenous vein smooth-muscle cells. J Cardiovasc Pharmacol 31 [Suppl 1]:S348-S350

    PubMed  CAS  Google Scholar 

  • Woods M, Mitchell JA, Wood EG, Barker S, Walcot NR, Rees GM, Warner TD (1999) Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme. Mol Pharmacol 55:902909

    PubMed  CAS  Google Scholar 

  • Wu-Wong JR, Budzik GP, Devine EM, Opgenorth TJ (1990) Characterization of endothelin-converting enzyme in rat lung. Biochem Biophys Res Commun 171:1291–1296

    PubMed  CAS  Google Scholar 

  • Wu-Wong JR, Chiou WJ, Opgenorth TJ (1993) Prolonged treatment by phosphoramidon modulates the number of endothelin receptors in cultured Swiss 3T3 fibroblasts. J Cardiovasc Pharmacol 22:S77-S80

    PubMed  Google Scholar 

  • Wu-Wong JR, Devine EM, Budzik GP, Opgenorth TJ (1991) Characterization and partial purification of ECE in rat lung. J Cardiovasc Pharmacol 17:520525

    Google Scholar 

  • Wypij DM, Nichols JS, Novak PJ, Stacy DL, Berman J, Wiseman JS (1992) Role of mast cell chymase in the extracellular processing of big-endothelin-1 to endothelin-1 in the perfused rat lung. Biochem Pharmacol 43:845–853

    PubMed  CAS  Google Scholar 

  • Xu D, Emoto N, Giaid A, Slaughter C, Kaw S, deWit D, Yanagisawa M (1994) ECE-1: A membrane-bound metalloprotease that catalyses the proteolytic activation of big endothelin-1. Cell 78:473–485

    PubMed  CAS  Google Scholar 

  • Yanagisawa H, Richardson JA, Yanagisawa M (1999) The role of ECE-2 in cardiac development revealed by double targeted disruption of ECE-1 and ECE-2 genes in mice. 6th Int Conf ETs (Montréal, QC, Canada) ET-6 abstract book p 38

    Google Scholar 

  • Yanagisawa H, Yanagisawa M, Kapur RP, Richardson JA, Williams SC, Clouthier DE, deWit D, Emoto N, Hammer RE (1998) Dual genetic pathways of endothelin-mediated intercellular signaling revealed by targeted disruption of endothelin-converting enzyme-1 gene. Development 125:825–836

    PubMed  CAS  Google Scholar 

  • Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    PubMed  CAS  Google Scholar 

  • Yang Q, Kawaguchi T, Battistini B, Sirois P (1997) Neutral endopeptidase degrades endothelins in guinea-pig tracheal epithelial cells. Inflamm Res 46:S171-S172

    PubMed  CAS  Google Scholar 

  • Yano M, Okada K, Takada J, Hioki Y, Matsuyama AK, Fukuroda T, Noguchi K, Nishikibe M, Ikemote F (1991) Endothelin-converting enzyme and its in vitro and in vivo inhibition. J Cardiovasc Pharmacol 17:S26-S28

    PubMed  CAS  Google Scholar 

  • Yorimitsu K, Moroi K, Inagaki N, Saito T, Masuda Y, Masaki T, Seino S, Kimura S (1995) Cloning and sequencing of a human endothelin-converting enzyme in renal adenocarcinoma (ACHN) cells producing endothelin-2. Biochem Biophys Res Comm 208:721–727

    PubMed  CAS  Google Scholar 

  • Yoshimura S,Tsurumi Y,Takase S, Okuhara M (1995) WS75624 A and B, new endothelin converting enzyme inhibitors isolated from Saccharothrix sp. No. 75624. II.Structure elucidation of WS75624 A and B. J Antibiot (Tokyo) 48:1073–1075

    CAS  Google Scholar 

Download references

Authors
  1. B. Battistini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Y. Jeng
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Cardiac, Vascular and Inflammation Research, The William Harvey Research Institute St. Barthomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK

    Timothy D. Warner Ph.D

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Battistini, B., Jeng, A.Y. (2001). Endothelin-Converting Enzyme Inhibitors and their Effects. In: Warner, T.D. (eds) Endothelin and Its Inhibitors. Handbook of Experimental Pharmacology, vol 152. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56899-2_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-56899-2_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63237-2

  • Online ISBN: 978-3-642-56899-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation