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Adrenomedullin in Cardiovascular Disease pp 17–40Cite as

Adrenomedullin Receptor and Signal Transduction

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Part of the book series: Basic Science for the Cardiologist ((BASC,volume 19))

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References

  • Aiyar N, Rand K, Elshourbagy N A, Zeng Z, Adamou JE, Bergsma, DJ, and Li Y (1996) A cDNA encoding the calcitonin gene-related peptide type 1 receptor. J Biol Chem 271:11325–11329.

    Article  PubMed  Google Scholar 

  • Albertin G, Carraro G, Pamigotto PP, Conconi MT, Ziolkowska A, Malendowicz LK, and Nussdorfer GG (2003) Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis. Int J Mol Med 11:635–639.

    PubMed  Google Scholar 

  • Aldecoa A, Gujer R, Fischer JA, and Bom W (2000) Mammalian calcitonin receptor-like receptor/receptor activity modifying protein complexes define calcitonin gene-related peptide and adrenomedullin receptors in Drosophila Schneider 2 cells. FEBS Lett 471:156–160.

    Article  PubMed  Google Scholar 

  • Benovic JL, Pike LJ, Cerione RA, Staniszewski C, Yoshimasa T, Codina J, Caron MG, and Lefkowitz RJ. (1985) Phosphorylation of the mammalian beta-adrenergic receptor by cyclic AMP-dependent protein kinase. Regulation of the rate of receptor phosphorylation and dephosphorylation by agonist occupancy and effects on coupling of the receptor to the stimulatory guanine nucleotide regulatory protein. J Biol Chem 260:7094–7101.

    PubMed  Google Scholar 

  • Bom W, Muff R, and Fischer JA. (2002) Functional interaction of G protein-coupled receptors of the adrenomedullin peptide family with accessory receptor-activity-modifying proteins (RAMP). Microsc Res Tech 57:14–22.

    Article  PubMed  Google Scholar 

  • Chini EN, Choi E, Grande JP, Bumett JC, and Dousa TP. (1995) Adrenomedullin suppresses mitogenesis in rat mesangial cells via cAMP pathway. Biochem Biophys Res Commun 215:868–873.

    Article  PubMed  Google Scholar 

  • Christopoulos G, Peny KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, Main MJ, Foord SM, and Sexton PM. (1999) Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol 56:235–242.

    PubMed  Google Scholar 

  • Coppock HA, Owji AA, Bloom SR, and Smith DM. (1996) A rat skeletal muscle cell line (L6) expresses specific adrenomedullin binding sites but activates adenylate cyclase via calcitonin gene-related peptide receptors. Biochem J 318:241–245.

    PubMed  Google Scholar 

  • Eguchi S, Hirata Y, Iwasaki H, Sato K, Watanabe TX, Inui T, Nakajima K, Sakakibara S, and Marunmo E. (1994a) Structure-activity relationship of adrenomedullin, a novel vasodilatory peptide, in cultured rat vascular smooth muscle cells. Endocrinology 135:2454–2458.

    Article  PubMed  Google Scholar 

  • Eguchi S, Hirata Y, Kano H, Sato K, Watanabe Y, Watanabe TX, Nakajima K, Sakakibara S, and Marumo E. (1994b) Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells. FEBS Lett 340:226–230.

    Article  PubMed  Google Scholar 

  • Elshourbagy NA, Adamou JE, Swift AM, Disa J, Mao J, Ganguly S, Bergsma DJ, and Aiyar N. (1998) Molecular cloning and characterization of the porcine calcitonin gene-related peptide receptor. Endocrinology 139:1678–1683.

    Article  PubMed  Google Scholar 

  • Entzeroth M, Doods HN, Wieland HA, and Wienen W. (1995) Adrenomedullin mediates vasodilation via CGRP1 receptors. Life Sci 56:PL19–25.

    Article  PubMed  Google Scholar 

  • Evans BN, Rosenblatt MI, Mnayer LO, Oliver KR, and Dickerson IM. (2000) CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors. J Biol Chem 275:31438–31443.

    Article  PubMed  Google Scholar 

  • Flahaut M, Rossier BC, and Firsov D. (2002) Respective roles of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP) in cell surface expression of CRLR/RAMP heterodimeric receptors. J Biol Chem 277:14731–14737.

    PubMed  Google Scholar 

  • Fluhmann B, Muff R, Hunziker W, Fischer JA, and Bom W. (1995) A human orphan calcitonin receptor-like structure. Biochem Biophys Res Commun 206:341–347.

    Article  PubMed  Google Scholar 

  • Fukai N, Shichiri M, Ozawa N, Matsushita M, and Hirata Y. (2003) Coexpression of calcitonin receptor-like receptor and receptor activity-modifying protein 2 or 3 mediates the antimigratory effect of adrenomedullin. Endocrinology 144:447–453.

    Article  PubMed  Google Scholar 

  • Gether U. (2000) Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev 21:90–113.

    Article  PubMed  Google Scholar 

  • Hall JM, Siney L, Lippton H, Hyman A, Kang-Chang J, and Brain SD. (1995) Interaction of human adrenomedullin 13–52 with calcitonin gene-related peptide receptors in the microvasculature of the rat and hamster. Br J Pharmacol 114:592–597.

    PubMed  Google Scholar 

  • Han ZQ, Coppock HA, Smith DM, Van Noorden S, Makgoba MW, Nicholl CG, and Legon S. (1997) The interaction of CGRP and adrenomedullin with a receptor expressed in the rat pulmonary vascular endothelium. J Mol Endocrinol 18:267–272.

    Article  PubMed  Google Scholar 

  • Hausdorff WP, Bouvier M, O’Dowd BF, Irons GP, Caron MG, and Lefkowitz RJ. (1989) Phosphorylation sites on two domains of the beta 2-adrenergic receptor are involved in distinct pathways of receptor desensitization. J Biol Chem 264:12657–12665.

    PubMed  Google Scholar 

  • Hilairet S, Foord SM, Marshall FH, and Bouvier M. (2001) Protein-protein interaction and not glycosylation determines the binding selectivity of heterodimers between the calcitonin receptor-like receptor and the receptor activity-modifying proteins. J Biol Chem 276:29575–29581.

    Article  PubMed  Google Scholar 

  • Hinson JP, Kapas S, and Smith DM. (2000) Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev 21:138–167.

    Article  PubMed  Google Scholar 

  • Hirata Y, Mitaka C, Sato K, Nagura T, Tsunoda Y, Amaha K, and Maummo F. (1996) Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis. J Clin Endocrinol Metab 81:1449–1453.

    Article  PubMed  Google Scholar 

  • Horio T, Kohno M, Kano H, Ikeda M, Yasunari K, Yokokawa K, Minami M, and Takeda T. (1995) Adrenomedullin as a novel antimigration factor of vascular smooth muscle cells. Circ Res 77:660–664.

    PubMed  Google Scholar 

  • Ishiyama Y, Kitamura K, Ichiki Y, Nakamura S, Kida O, Kangawa K, and Eto T. (1993) Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats. Eur J Pharmacol 241:271–273.

    Article  PubMed  Google Scholar 

  • Iwasaki H, Eguchi S, Shichiri M, Marumo F, and Hirata Y. (1998a) Adrenomedullinm as a novel growth-promoting factor for cultured vascular smooth muscle cells: role of tyrosine kinase-mediated mitogen-activated protein kinase activation. Endocrinology 139:3432–3441.

    Article  PubMed  Google Scholar 

  • Iwasaki H, Eguchi S, Shichiri M, Manuio F, and Hirata Y. (1998b) Down-regulation of adenylate cyclase coupled to adrenomedullin receptor in vascular smooth muscle cells. Eur J Pharmacol 352:131–134.

    Article  PubMed  Google Scholar 

  • Iwasaki H, Shichiri M, Marumo F, and Hirata Y. (2001) Adrenomedullin stimulates proline-rich tyrosine kinase 2 in vascular smooth muscle cells. Endocrinology 142:564–572.

    Article  PubMed  Google Scholar 

  • Kano H, Kohno M, Yasunari K, Yokokawa K, Horio T, Ikeda M, Minami M, Hanehira T, Takeda T, and Yoshikawa J. (1996) Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells. J Hypertens 14:209–213.

    PubMed  Google Scholar 

  • Kapas S, Brown DW, Farthing PM, and Hagi-Pavli E. (1997) Adrenomedullin has mitogenic effects on human oral keratinocytes: involvement of cyclic AMP. FEBS Lett 418:287–290.

    Article  PubMed  Google Scholar 

  • Kato H, Shichiri M, Manuno F, and Hirata Y (1997) Adrenomedullin as an autocrine/paracrine apoptosis survival factor for rat endothelial cells. Endocrinology 138:2615–2620.

    Article  PubMed  Google Scholar 

  • Kim W, Moon SO, Sung MJ, Kim SH, Lee S, So JN, and Park SK. (2003) Angiogenic role of adrenomedullin through activation of Akt, mitogen-activated protein kinase, and focal adhesion kinase in endothelial cells. FASEB J 17:1937–1939.

    PubMed  Google Scholar 

  • Kitamura K, Kangawa K, and Eto T. (2002) Adrenomedullin and PAMP: discovery, structures, and cardiovascular functions. Microsc Res Tech 57:3–13.

    Article  PubMed  Google Scholar 

  • Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, and Eto T. (1993) Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 192:553–560.

    Article  PubMed  Google Scholar 

  • Kohno M, Yokokawa K, Kano H, Yasunari K, Minami M, Hanehira T, and Yoshikawa J. (1997) Adrenomedullin is a potent inhibitor of angiotensin II-induced migration of human coronary artery smooth muscle cells. Hypertension 29:1309–1313.

    PubMed  Google Scholar 

  • Kohno M, Yasunari K, Minami M, Kano H, Maeda K, Mandel AK, Inoki K, Haneda M, and Yoshikawa J. (1999) Regulation of rat mesangial cell migration by platelet-derived growth factor, angiotensin II, and adrenomedullin. J Am Soc Nephrol 10:2495–2502.

    PubMed  Google Scholar 

  • Leuthauser K, Gujer R, Aldecoa A, McKinney RA, Muff R, Fischer JA, and Bom W (2000) Receptor-activity-modifying protein 1 forms heterodimers with two G-protein-coupled receptors to define ligand recognition. Biochem J 351:347–351.

    Article  PubMed  Google Scholar 

  • Lin HY, Hams TL, Flannery MS, Aruffo A, Kaji EH, Gom A, Kolakowski LF Jr., Lodish HF, and Goldring SR. (1991) Expression cloning of an adenylate cyclase-coupled calcitonin receptor. Science 254:1022–1024.

    PubMed  Google Scholar 

  • Luebke AE, Dahll GP, Roos BA, and Dickerson IM. (1996) Identification of a protein that confers calcitonin gene-related peptide responsiveness to oocytes by using a cystic fibrosis transmembrane conductance regulator assay. Proc Natl Acad Sci U S A 93:3455–3460.

    Article  PubMed  Google Scholar 

  • Martinez A, Elsasser TH, Muro-Cacho C, Moody TW, Miller MJ, Macri CJ, and Cuttitta F. (1997) Expression of adrenomedullin and its receptor in normal and malignant human skin: a potential pluripotent role in the integument. Endocrinology 138:5597–5604.

    Article  PubMed  Google Scholar 

  • McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, and Foord SM. (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393:333–339.

    Article  PubMed  Google Scholar 

  • Miller MI, Martinez A, Unsworth EJ, Thiele CJ, Moody TW, Elsasser T, and Cuttitta F. (1996) Adrenomedullin expression in human tumor celi lines. Its potential role as an autocrine growth factor. J Biol Chem 271:23345–23351.

    Article  PubMed  Google Scholar 

  • Muff R, Buhlmann N, Fischer JA, and Bom W. (1999) An amylin receptor is revealed following co-transfection of a calcitonin receptor with receptor activity modifying proteins-1 or-3. Endocrinology 140: 2924–2927.

    Article  PubMed  Google Scholar 

  • Nishimatsu H, Suzuki E, Nagata D, Moriyama N, Satonaka H, Walsh K, Sata M, Kangawa K, Matsuo H, Goto A, Kitamura T, and Hirata Y. (2001) Adrenomedullin induces endothelium-dependent vasorelaxation via the phosphatidylinositol 3-kinase/Akt-dependent pathway in rat aorta. Circ Res 89:63–70.

    PubMed  Google Scholar 

  • Njuki F, Nicholl CG, Howard A, Mak JC, Bames PJ, Girgis SI, and Legon S. (1993) A new calcitonin-receptor-like sequence in rat pulmonaiy blood vessels. Clin Sci (Lond) 85:385–388.

    Google Scholar 

  • Nuki C, Kawasaki H, Kitamura K, Takenaga M, Kangawa K, Eto T, and Wada A. (1993) Vasodilator effect of adrenomedullin and calcitonin gene-related peptide receptors in rat mesenteric vascular beds. Biochem Biophys Res Commun 196:245–251.

    Article  PubMed  Google Scholar 

  • Nussdorfer GG, Rossi GP, and Mazzocchi G. (1997) Role of adrenomedullin and related peptides in the regulation of the hypothalamo-pituitary-adrenal axis. Peptides 18:1079–1089.

    Article  PubMed  Google Scholar 

  • Oehler MK, Norbury C, Hague S, Rees MC, and Bicknell R. (2001) Adrenomedullin inhibits hypoxic celi death by upregulation of Bcl-2 in endometrial cancer cells: a possible promotion mechanism for tumour growth. Oncogene 20:2937–2945.

    Article  PubMed  Google Scholar 

  • Okumura H, Nagaya N, Itoh T, Okano I, Hino J, Mori K, Tsukamoto Y, Ishibashi-Ueda H, Miwa S, Tambara K, Toyokuni S, Yunati C, and Kangawa K. (2004) Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injuty through the phosphatidylinositol 3-kinase/Akt-dependentpathway. Circulation 109:242–248.

    Article  PubMed  Google Scholar 

  • Owji AA, Gardiner JV, Upton PD, Mahmoodi M, Ghatei MA, Bloom SR, and Smith DM. (1996) Characterisation and molecular identification of adrenomedullin binding sites in the rat spinal cord: a comparison with calcitonin gene-related peptide receptors. J Neurochem 67:2172–2179.

    PubMed  Google Scholar 

  • Owji AA, Smith DM, Coppock HA, Morgan DG, Bhogal R, Ghatei MA, and Bloom SR. (1995) An abundant and specific binding site for the novel vasodilator adrenomedullin in the rat. Endocrinology 136:2127–2134.

    Article  PubMed  Google Scholar 

  • Parkes DG, and May CN. (1997) Direct cardiac and vascular actions of adrenomedullin in conscious sheep. Br J Pharmacol 120:1179–1185.

    PubMed  Google Scholar 

  • Pelengaris S, Khan M, and Evan G. (2002) c-MYC: more than just a matter of life and death. Nat Rev Cancer 2:764–776.

    Article  PubMed  Google Scholar 

  • Poyner DR, Sexton P M, Marshall I, Smith DM, Quirion R, Bom W, Muff R, Fischer JA, and Foord SM. (2002) Intemational Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev 54:233–246.

    Article  PubMed  Google Scholar 

  • Prado MA, Evans-Bain B, Oliver KR, and Dickerson IM. (2001) The role of the CGRP-receptor component protein (RCP) in adrenomedullin receptor signal transduction. Peptides 22:1773–1781.

    Article  PubMed  Google Scholar 

  • Rebuffat P, Fomens ML, Aragona F, Ziolkowska A, Malendowicz LK, and Nussdorfer GG. (2002) Adrenomedullin and its receptors are expressed in the zona glomerulosa of human adrenal gland: evidence that ADM enhances proliferation and decreases apoptosis in cultured ZG cells. Int J Mol Med 9:119–124.

    PubMed  Google Scholar 

  • Segawa K, Minami K, Sata T, Kuroiwa A, and Shigematsu A. (1996) Inhibitory effect of adrenomedullin on rat mesangial cell mitogenesis. Nephron 74:577–579.

    PubMed  Google Scholar 

  • Shichiri M, Fukai N, Ozawa N, Iwasaki H, and Hirata Y (2003) Adrenomedullin is an autocrine/paracrine growth factor for rat vascular smooth muscle cells. Regul Pept 112:167–173.

    Article  PubMed  Google Scholar 

  • Shichiri M, and Hirata Y (2003) Regulation of cell growth and apoptosis by adrenomedullin. Hypertens Res 26:S9–14.

    PubMed  Google Scholar 

  • Shichiri M, Kato H, Doi M, Marumo F, and Hirata Y (1999) Induction of max by adrenomedullin and calcitonin gene-related peptide antagonizes endothelial apoptosis. Mol Endocrinol 13:1353–1363.

    Article  PubMed  Google Scholar 

  • Shimekake Y, Nagata K, Ohta S, Kambayashi Y, Teraoka H, Kitamura K, Eto T, Kangawa K, and Matsuo H. (1995) Adrenomedullin stimulates two signal transduction pathways, cAMP accumulation and Ca2+ mobilization, in bovine aortic endothelial cells. J Biol Chem 270:4412–4417.

    Article  PubMed  Google Scholar 

  • Shimosawa T, Shibasaki Y, Ishibashi K, Kitamura K, Kangawa K, Kato S, Ando K, and Fujita T. (2002) Adrenomedullin, an endogenous peptide, counteracts cardiovascular damage. Circulation 105:106–111.

    Article  PubMed  Google Scholar 

  • Shindo T, Kurihara Y, Nishimatsu H, Monyama N, Kakoki M, Wang Y, Imai Y, Ebihara A, Kuwaki T, Ju KH, Minamino N, Kangawa K, Ishikawa T, Fukuda M, Akimoto Y, Kawakami H, Imai T, Monta H, Yazaki Y, Nagai R, Hirata Y, and Kurihara H. (2001) Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene. Circulation 104:1964–1971.

    PubMed  Google Scholar 

  • Sugo S, Minamino N, Shoji H, Kangawa K, Kitamura K, Eto T, and Matsuo H. (1995) Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. Biochem Biophys Res Commun 207:25–32.

    Article  PubMed  Google Scholar 

  • Takahashi K, Satoh F, Hara E, Murakami O, Kumabe T, Tominaga T, Kayama T, Yoshimoto T, and Shibahara S. (1997a) Production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells. J Neurochem 68:726–731.

    PubMed  Google Scholar 

  • Takahashi K, Satoh F, Hara E, Sone M, Murakami O, Kayama T, Yoshimoto T, and Shibahara S. (1997b) Production and secretion of adrenomedullin from glial cell tumors and its effects on cAMP production. Peptides 18:1117–1124.

    Article  PubMed  Google Scholar 

  • Togawa M, Haneda M, Araki S, Sugimoto T, Isono M, Hidaka H, Yasuda H, Kashiwagi A, and Kikkawa R (1997) Beraprost sodium, an analogue of prostacyclin, induces the expression of mitogen-activated protein kinase phosphatase and inhibits the proliferation of cultured mesangial cells. Eur J Pharmacol 336:291–294.

    Article  PubMed  Google Scholar 

  • Wang HY, Hadcock JR, and Malbon CC. (1990) Beta-adrenergic receptor regulation. New insights on biochemical and molecular mechanisms. Receptor 1:13–32.

    PubMed  Google Scholar 

  • Withers DJ., Coppock HA., Seufferlein T, Smith DM, Bloom SR, and Rozengurt E. (1996) Adrenomedullin stimulates DNA synthesis and cell proliferation via elevation of cAMP in Swiss 3T3 cells. FEBS Lett 378:83–87.

    Article  PubMed  Google Scholar 

  • Yin H, Chao L, and Chao J. (2004) Adrenomedullin protects against myocardial apoptosis after ischemia/reperfusion through activation of Akt-GSK signaling. Hypertension 43:109–116.

    Article  PubMed  Google Scholar 

  • Ym X, Grove L, and Prochownik EV. (1998) Lack of transcriptional repression by maxhomodimers. Oncogene 16:2629–2637.

    Article  PubMed  Google Scholar 

  • Yoshimoto T, Fukai N, Sato R, Sugiyama T, Ozawa N, Shichiri M, and Hirata Y. (2004) Anti-oxidant effect of adrenomedullin on angiotensin II-induced ROS generation in vascular smooth muscle cells. Endocrinology 145:3331–3337.

    Article  PubMed  Google Scholar 

  • Zimmermann U, Fischer JA, and Muff R. (1995) Adrenomedullin and calcitonin gene-related peptide interact with the same receptor in cultured human neuroblastoma SK-N-MC cells. Peptides 16:421–424.

    Article  PubMed  Google Scholar 

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  1. Deparanent of Clinical and Molecular Endocinology, Tokyo Medical and Deatal Univrsity Graduate School, Tokyo, Japan

    Takanobu Yoshimoto & Yukio Hirata

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  1. Takanobu Yoshimoto
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  2. Yukio Hirata
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  1. Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi, Japan

    Toshio Nishikimi MD, PhD

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Yoshimoto, T., Hirata, Y. (2005). Adrenomedullin Receptor and Signal Transduction. In: Nishikimi, T. (eds) Adrenomedullin in Cardiovascular Disease. Basic Science for the Cardiologist, vol 19. Springer, Boston, MA. https://doi.org/10.1007/0-387-25405-6_2

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