Advertisement

Das Renin-Angiotensin-System, Molekularbiologie und Pharmakologie — Was gibt es Neues?

  • N. Niedermaier
  • M. Feldmer
  • D. Ganten
Conference paper
  • 11 Downloads

Zusammenfassung

Das Renin-Angiotensin-System (RAS) ist ein wichtiges Effektorsystem in der Regulation des Blutdrucks und der Salz- und Wasserhomöostase. Das Glykoprotein Angiotensinogen ist hierbei der Ausgangspunkt: das Protein wird in der Leber synthetisiert und in das Blut abgegeben, wo es das Substrat für Renin darstellt. Renin wird von den juxtaglomerulären Zellen der Niere synthetisiert, gespeichert und sezerniert, und spaltet von Angiotensinogen das Dekapeptid Angiotensin I ab. Angiotensin I wird schließlich durch eine Dipeptidylpeptidase (Angiotensin-Konvertingenzym) in das Effektorpeptid des RAS, das Angiotensin II überführt (Abb. 1).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Ahlenc-Gelas F, Soubrier F, Hubert C, Allegrini J, John M, Tregear G, Corvol P (1988) Molecular cloning and complete aminoacid sequence of human angiotensin I converting enzyme. Hypertension 12: 340 (Abstract)Google Scholar
  2. 2.
    Bernstein KE, Martin BM, Bernstein EA, Linton J, Striker L, Striker G (1988) The isolation of angiotensin converting enzyme cDNA. J Biol Chem 263:11 021–11 024Google Scholar
  3. 3.
    Brasier AR, Tate JE, Ron D, Habener J (1989) Multiple cis-acting DNA regulatory elements mediate hepatic angiotensinogen gene expression. Mol Endocrinol 3: 10221034Google Scholar
  4. 4.
    Burnham CE, Hawelu-Johnson CL, Frank BM, Lynch KR (1987) Molecular cloning of rat renin cDNA and its gene. Proc Natl Acad Sci USA 84: 5605–5609PubMedCrossRefGoogle Scholar
  5. 5.
    Campbell DJ, Habener JF (1986) Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest 79: 31–39CrossRefGoogle Scholar
  6. 6.
    Campbell DJ, Habener JF (1987) Cellular localization of angiotensinogen gene expression in brown adipose tissue and mesentery: Quantification of messenger ribonucleic acid abundance using hybridization in situ. Endocrinology 121: 1616–1626Google Scholar
  7. 7.
    Chiu AT, McCall DE, Nguyen TT et al. (1989) Discrimination of angiotensin II receptor subtypes by dithiothreitol. EJP 170: 117–118Google Scholar
  8. 8.
    Cohens S, Taylor JM, Murakami K, Michelakis AM, Inagami T (1972) Isolation and characterization of renin like enzymes from mouse submaxillary glands. Biochemistry 11: 4286–4293CrossRefGoogle Scholar
  9. 9.
    Doolitle RF (1983) Angiotensinogen is related to the antitrypsin-antithrombin-ovalbumin family. Science 222: 417–419CrossRefGoogle Scholar
  10. 10.
    Dzau VJ, Slater EE, Haber E (1979) Complete purification of dog renal renin. Biochemistry 18: 5224–5228PubMedCrossRefGoogle Scholar
  11. 11.
    Feldmer M (1990) Diplomarbeit Biologie, Universität Heidelberg (Institut für Pharmakologie)Google Scholar
  12. 12.
    Field LJ, McGowan RA, Dickinson DP, Gross KW (1984) Tissue and gene specifity of mouse renin expression. Hypertension 6: 597–603PubMedCrossRefGoogle Scholar
  13. 13.
    Field LJ, Philbrick WM, Howles PN, Dickinson DP, McGowan RA, Gross KW (1984) Expression of tissue specific Ren-1 and ren-2 genes in mice: comparative analysis of 5’ proximal flanking regions. Mol Cell Biol 4: 2321–2331PubMedGoogle Scholar
  14. 14.
    Frossard PM, Gonzales PA, Fritz LC, Ponte PA, Fiddes JC, Atlas SA (1986) Two PFLP’s at the human renin (ren) gene locus. Nucleic Acids Res 14: 4380Google Scholar
  15. 15.
    Hackenthal E, Klett C, Münter K (1988) Control of angiotensinogen synthesis and secretion by the liver. Med Sci Res 16: 7–10Google Scholar
  16. 16.
    Hardman JA, Hort YJ, Cantanzaro DF, Tellan JT, Baxter JD, Morris BJ, Shine J (1984) Primary structure of the human renin gene. DNA 3: 457–468PubMedCrossRefGoogle Scholar
  17. 17.
    Held WA, Mullins JJ, Kuhn NJ, Gallagher JF, Gu GD, Gross T (1989) T antigen expression and tumorigenesis in transgenic mice containing a mouse major urinary protein SV 40 T antigen hybrid gene. EMBO J 8: 183–191PubMedGoogle Scholar
  18. 18.
    Hellman W, Suzuki F, Ohkubo H, Nakanishi S, Ludwig G, Ganten D (1988) Angiotensinogen gene expression in extrahepatic rat tissues. Application of a solution hybridization assay. Naunyn-Schmiedebergs Arch Pharmacol 338: 327–331Google Scholar
  19. 19.
    Herrmann HC, Dzau VJ (1983) The feedback regulation of angiotensinogen production by components of the renin-angiotensin system. Circ Res 52: 328–334PubMedCrossRefGoogle Scholar
  20. 20.
    Herrmann HC, Morris BJ, Reid IA (1980) Effect of angiotensin II and sodium depletion on angiotensinogen production. Am J Physiol 238: E 145—E 149Google Scholar
  21. 21.
    Hobart PM, Fogliano M, O’Connor BA, Schaefer IM, Chirgwin JM (1984) Human renin gene: structure and sequence analysis. Proc Nat Acad Sci USA 81: 5026–5030PubMedCrossRefGoogle Scholar
  22. 22.
    Ingelfinger JR, Pratt RE, Ellison K, Dzau VJ (1986) Sodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla. J Clin Invest 78: 1311–1315PubMedCrossRefGoogle Scholar
  23. 23.
    Klett C, Hackenthal E (1987) Induction of angiotensinogen synthesis and secretion by angiotensin II. Clin Exp Hypert A9: 2027–2047CrossRefGoogle Scholar
  24. 24.
    Klett C, Hellmann T, Müller F, Suzuki F, Nakanishi S, Ohkubo H, Ganten D, Hackenthal E (1988) Angiotensin II controls angiotensinogen secretion at a pretranslational level. J Hypertens 6 (Suppl 4) S 442—S 445Google Scholar
  25. 25.
    Klett C, Hellmann W, Suzuki F, Nakanishi S, Ohrubo H, Ganten D, Hackenthal E (1988) Induction of angiotensinogen mRNA in hepatocytes by angiotensin II and glucocorticoids. Clin Exp Hypert A10: 1009–1022Google Scholar
  26. 26.
    Lindpaintner K, Takahashi S, Metzger R, Murakami K, Ganten D (1988) Restriction fragment length polymorphism (RFLP) of the renin gene distinguishes hypertensive and normotensive rat strains. Hypertension 12: 359 (Abstract)Google Scholar
  27. 27.
    Lloyd CJ, Cary DA, Mendelsohn FAO (1987) Angiotensin converting enzyme induction by cyclic AMP and analogues in cultured endothelial cells. Mol Cell Endocrinol 52: 219225Google Scholar
  28. 28.
    Mendelsohn FAO, Lloyd CJ, Kachel C, Funder JW (1982) Induction by glucocorticoids of antiogensin converting enzyme production from bovine endothelial cells in culture and rat lung in vivo. J Clin Invest 70: 684–692PubMedCrossRefGoogle Scholar
  29. 29.
    Metsaerinne K, Rosenloef K, Groenhagen-Riska C, Fyhrquist F (1988) Direct radio-immunoassay of renin substrate: effect of converting enzyme inhibition. Scand J Clin Lab Inves 48: 131–136Google Scholar
  30. 30.
    Morris BJ (1986) New possibilities for intracellular renin and inactive renin now that the structure of the human renin gene has been elucidated. Clin Sci 71: 345–355PubMedGoogle Scholar
  31. 31.
    Mullins JJ, Burt DW, Windass JD, McTurk P, George H, Brammer WJ (1982) Molecular cloning of two distinct renin genes from the DBA/2 mouse. EMBO J 1: 1461–1466PubMedGoogle Scholar
  32. 32.
    Mullins JJ, Sigmund DD, Kane-Haas C, Wu C, Pacholec F, Zeng Q, Gross KW (1988) Studies on the regulation of renin genes using transgenic mice. Clin Exp Hypert A 10: 1157–1167Google Scholar
  33. 33.
    Naftilan AJ, Burt D, Paul M, Pratt RE, Leppert M, White R, Williams R, Hobart P, Chirgwin J, Dzau VJ (1987) Identification and localization of four restriction fragment length polymorphisms ( RFLP) in the human renin gene. Clin Res 35: 445AGoogle Scholar
  34. 34.
    Nasjleti A, Masson GMC (1973) Stimulation of angiotensinogen formation by renin and angiotensinogen. Proc Soc Exp Biol Med 142: 307–310CrossRefGoogle Scholar
  35. 35.
    Ohkubo H, Kageyama R, Ujihara M, Hirose T, Inayama S, Nakanishi S (1983) Cloning and sequence analysis of cDNA for rat angiotensinogen. Proc Nat Acad Sci USA 80: 2196–2200PubMedCrossRefGoogle Scholar
  36. 36.
    Paul M, Burt DW, Nakamura N, Dzau VJ (1988) Tissue specifity of renin promotor activity in the mouse. Hypertension 12: 339, A27 (Abstract)Google Scholar
  37. 37.
    Rapp JP, Wang SM, Dene H (1989) A genetic polymorphism in the renin gene of Dahl rats cosegregates with blood pressure. Science 243: 542–544PubMedCrossRefGoogle Scholar
  38. 38.
    Sernia C, Reid IA (1980) Stimulation of angiotensinogen production: a dose related effect of angiotensin II in the conscious dog. Am J Physiol 239: E 442–446Google Scholar
  39. 39.
    Soubrier F, Panthier JJ, Houot A-M, Rougeon F, Corvol P (1986) Segmental homology between the promotor region of the human renin gene and the mouse ren 1 and ren 2 promotor regions. Gene 41: 85–92PubMedCrossRefGoogle Scholar
  40. 40.
    Stuzman M, Radziwill R, Komischke K, Klett C, Hackenthal E (1986) Hormonal and pharmacological alteration of angiotensinogen secretion from rat hepatocytes. Biochim Biophys Acta 886: 48–56CrossRefGoogle Scholar
  41. 41.
    Tanaka T, Ohkubo H, Nakanishi S (1984) Common structural organization of the angiotensinogen and a-1 antitrypsin genes. J Biol Chem 259: 8063–8065PubMedGoogle Scholar
  42. 42.
    Tronik D, Dreyfus M, Babinet C, Rougeon F (1987) Regulated expression of the Ren-2 gene in transgenic mice derived from parenteral strains carrying only the Ren-1 gene. Embo J 6: 983–987PubMedGoogle Scholar
  43. 43.
    Wilson CM, Ward DE, Erdos EG, Gecse A (1976) Studies on membrane-bound renin in the mouse and rat. Circ Res 38 (Suppl II):II-95—II-98Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • N. Niedermaier
  • M. Feldmer
  • D. Ganten

There are no affiliations available

Personalised recommendations