Pflügers Archiv

, Volume 389, Issue 1, pp 29–35 | Cite as

Secretin and VIP-stimulated adenylate cyclase from rat heart

II. Impairment in spontaneous hypertension
  • Pierre Chatelain
  • Patrick Robberecht
  • Philippe De Neef
  • Jean-Claude Camus
  • Danielle Heuse
  • Jean Christophe
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


Cardiac adenylate cyclase activity was normal in 3 weeks-old spontaneously hypertensive rats of the Wistar-Okamoto substrain. The hormone-sensitive adenylate cyclase activity was reduced in 10 weeks-old or older animals, and secretin- and VIP-activations were definitely more impaired (by 64% and 69%, respectively) than isoproterenol- and glucagonactivation (17% and 22%, respectively). By contrast, the fluoride- and p[NH]ppG-stimulations of the enzyme were unaffected. These alterations in the adenylate cyclase system coupled to secretin and VIP appeared specific to the heart as the isolated pancreatic acinar cells from spontaneously hypertensive animals responded normally to secretin, as a liver particulate fraction responded normally to secretin and VIP, and both brain synaptic membranes and a particulate fraction of anterior pituitary to VIP.

Key words

Secretin Vasoactive intestinal peptide Glucagon Isoproterenol Adenylate cyclase Heart Spontaneously hypertensive rat 



vasoactive intestinal peptide

cyclic AMP

cyclic adenosine 3′∶5′-monophosphate


guanosine 5′-(β, γ-imido)triphosphate


ethylene-glycol-bis-(2-amino-ether)-N,N,N′,N′-tetraacetic acid




Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amer MS, Doba N, Reis DJ (1975) Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension. Proc. Natl Acad Sci USA 72:2135–2139Google Scholar
  2. Amsterdam A, Jamieson JD (1974) Studies on dispersed pancreatic exocrine cells. I. Dissociation technique and morphologic characteristics of separated cells. J Cell Biol 63:1037–1056Google Scholar
  3. Bakardjieva A, Galla HJ, Helmreich EJM (1979) Modulation of the β-receptor adenylate cyclase interactions in cultured Chang liver cells by phospholipid enrichment. Biochemistry 18:3016–3023Google Scholar
  4. Bataille D, Besson J, Laburthe M, Rosselin G (1977) Specificity in hormone-receptor interaction: studies with insulin, glucagon and vasoactive intestinal peptide (VIP). In: Bonfils S, Fromageot P, Rosselin G (eds) North-Holland Publishing Company, Amsterdam, p 113Google Scholar
  5. Bhalla RC, Ashley T (1978) Altered function of adenylate cyclase in the myocardium of the spontaneously hypertensive rat. Biochem Pharmacol 27:1967–1971Google Scholar
  6. Bhalla RC, Sharma RV, Ashley T (1978) Adenylate cyclase activity in myocardium of spontaneously hypertensive rat: effect of endogenous factors and solubilization. Biochem Biophys Res Commun 82:273–280Google Scholar
  7. Catt KJ, Harwood JP, Aguilera G, Dufau ML (1979) Hormonal regulation of peptide receptors and target cell response. Nature 280:109–116Google Scholar
  8. Chatelain P, Robberecht P, De Neef P, Claeys M, Christophe J (1979) Low responsiveness of cardiac adenylate cyclase activity to peptide hormones in spontaneously hypertensive rats. FEBS Lett 107:86–90Google Scholar
  9. Chatelain P, Robberecht P, De Neef P, Deschodt-Lanckman M, König W, Christophe J (1980) Secretin and VIP-stimulated adenylate cyclase from rat heart. I. General properties and structural requirements for enzyme activation. Pflügers Arch 389:21–27Google Scholar
  10. Christophe J, Conlon TP, Gardner JD (1976) Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig: binding of radioiodinated peptide. J Biol Chem 251:4629–4634Google Scholar
  11. Christophe J, De Neef P, Deschodt-Lanckman M, Robberecht P (1978) The interaction of caerulein with the rat pancreas. II. Specific binding of3H-caerulein on dispersed acinar cells. Eur J Biochem 91:31–38Google Scholar
  12. Cutillatta AF, Erinoff L, Heller A, Low J, Oparil S (1977) Development of left ventricular hypertrophy in young spontaneously hypertensive rats after peripheral sympathectomy. Circ Res 40:428–434Google Scholar
  13. Desbuquois B (1974) The interaction of vasoactive intestinal polypeptide and secretin with liver-cell membranes. Eur J Biochem 46:439–450Google Scholar
  14. Deschodt-Lanckman M, Robberecht P, Christophe J (1977) Characterization of VIP-sensitive adenylate cyclase in guinea pig brain. FEBS Lett 83:76–80Google Scholar
  15. Fahrenkrug J (1979) Vasoactive intestinal polypeptide: measurement, distribution and putative neurotransmitter function. Digestion 19:149–169Google Scholar
  16. Gardner JD, Conlon TP, Adams TD (1976) Cyclic AMP in pancreatic acinar cells: effects of gastrointestinal hormones. Gastroenterology 70:29–35Google Scholar
  17. Gilman AG (1970) A protein binding assay for adenosine 3′∶5′-cyclic monophosphate. Proc Natl Acad Sci USA 67:305–312Google Scholar
  18. Gourdji D, Bataille D, Vauclin N, Grouselle D, Rosselin G, Tixier-Vidal A (1979) Vasoactive intestinal peptide (VIP) stimulates prolactin (PRL) release and cAMP production in a rat pituitary cell line (GH3/B6). Additive effects of VIP and TRH on PRL release. FEBS Lett 104:165–168Google Scholar
  19. Harwood JP, Conti M, Conn PM, Dufau ML, Catt KJ (1978) Receptor regulation and target cell responses: studies in the ovarian luteal cell. Mol Cell Endocrinol 11:121–135Google Scholar
  20. Iams SG, McMurtry JP, Wexler BC (1979) Aldosterone, deoxycorticosterone, corticosterone, and prolactin changes during the lifespan of chronically and spontaneously hypertensive rats. Endocrinology 104:1357–1363Google Scholar
  21. Lesniak MA, Roth J (1976) Regulation of receptor concentration by homologous hormone. Effect of human growth hormone on its receptor in IM-9 lymphocytes. J Biol Chem 251:3720–3729Google Scholar
  22. Limas C, Limas CJ (1978) Reduced number of β-adrenergic receptors in the myocardium of spontaneously hypertensive rats. Biochem Biophys Res Commun 83:710–714Google Scholar
  23. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  24. Lundberg JM, Hökfelt T, Kewenter J, Pettersson G, Ahlamn H, Edin R, Dahlström A, Nilsson G, Terenius L, Uvnäs-Wallensten K, Said S (1979) Substance P-, VIP-, and enkephalin-like immunoreactivity in the human vagus nerve. Gastroenterology 77:468–471Google Scholar
  25. Neville DM Jr, Kahn CR (1974) Isolation of plasma membranes for cell surface membrane receptor studies. Methods Membr Biol 4:57–88Google Scholar
  26. Robberecht P, Conlon TP, Gardner JD (1976) Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig: structural requirements for effects of vasoactive intestinal peptide and secretin on cellular adenosine 3′∶5′-monophosphate. J Biol Chem 251:4635–4639Google Scholar
  27. Robberecht P, De Neef P, Lammens M, Deschodt-Lanckman M, Christophe J (1978) Specific binding of vasoactive intestinal peptide to brain membranes from the guinea pig. Eur J Biochem 90:147–154Google Scholar
  28. Robberecht P, De Neef P, Lammens M, Christophe J, Koenig W (1979a) The secretin(Sn)- and VIP-receptors of the rat pancreas. Gastroenterol Clin Biol 3:294–295Google Scholar
  29. Robberecht P, Deschodt-Lanckman M, Camus JC, De Neef P, Lambert M, Christophe J (1979b) VIP activation of rat anterior pituitary adenylate cyclase. FEBS Lett 103:229–233Google Scholar
  30. Saavedra JM, Grobecker H, Axelrod J (1978) Changes in central catecholaminergic neurons in the spontaneously (genetic) hypertensive rat. Circ Res 42:529–534Google Scholar
  31. Salomon Y, Londos C, Rodbell M (1974) A highly sensitive adenylate cyclase assay. Anal Biochem 58:541–548Google Scholar
  32. Sen S, Tarazi RC, Bumpus FM (1976) Biochemical changes associated with development and reversal of cardiac hypertrophy in spontaneously hypertensive rats. Cardiovasc Res 10:254–261Google Scholar
  33. Snyder FF, Drummond GI (1978) Activation and stabilization of cardiac adenylate cyclase by GTP analog and fluoride. Arch Biochem Biophys 185:116–125Google Scholar
  34. Sowers JR, Tempel G, Resch G, Colantino M (1978) Pituitary response to TRH and LHRH in spontaneously hypertensive rats. Proc Soc Exp Biol Med 159:397–399Google Scholar
  35. Srikant CB, Freeman D, McCorkle K, Unger RH (1977) Binding and biologic activity of glucagon in liver cell membranes of chronically hyperglucagonemic rats. J Biol Chem 252:7434–7436Google Scholar
  36. Svoboda M, Robberecht P, Camus J, Deschodt-Lanckman M, Christophe J (1976) Subcellular distribution and response to gastrointestinal hormones of adenylate cyclase in the rat pancreas. Partial purification of a stable plasma membrane preparation. Eur J Biochem 69:185–193Google Scholar
  37. Weiss L, Lundgren Y (1978) Left ventricular hypertrophy and its reversibility in young spontaneously hypertensive rats. Cardiovasc Res 12:635–638Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Pierre Chatelain
    • 1
  • Patrick Robberecht
    • 1
  • Philippe De Neef
    • 1
  • Jean-Claude Camus
    • 1
  • Danielle Heuse
    • 1
  • Jean Christophe
    • 1
  1. 1.Department of Biochemistry and Nutrition, Medical SchoolUniversité Libre de BruxellesBrusselsBelgium

Personalised recommendations