Abstract
Membrane adenylate cyclase from rat heart was activated by the two gut peptides secretin and vasoactive intestinal peptide (VIP), glucagon, and the β-adrenergic drug isoproterenol, in the presence of guanosine 5′-triphosphate (GTP). With all the stimuli tested, the optimal magnesium concentration was 5 mM, i.e. in excess over the 0.5 mM ATP substrate concentration and 0.01 mM GTP used as cofactor. Under these conditions, half-maximal adenylate cyclase activation with glucagon, secretin, and VIP was achieved at concentrations of 0.5, 0.5 and 1.0 μM, respectively. Data obtained with the secretin (7–27) fragment, a secretin antagonist, indicate that secretin and VIP acted on the same binding sites, which differed from glucagon binding sites. Structural requirements for secretin activation of cardiac adenylate cyclase were evaluated by comparing the potency and efficacy of parent peptides and synthetic analogs. The gastric inhibitory peptide GIP was inactive. When using 13 mono-or bi-substituted analogs, it appeared that amino acids in positions 1, 2, 3, 4 and 6 were of major importance while those in position 5 and 11 played a relatively minor role.
Similar content being viewed by others
Abbreviations
- VIP:
-
vasoactive intestinal peptide
- GIP:
-
gastric inhibitory peptide
- Sn:
-
secretin
- cyclic AMP:
-
cyclic adenosine 3′:5′-monophosphate
- EGTA:
-
ethylene-glycol-bis-(2-aminoethylether)-N,N,N′,N′-tetraacetic acid
- Enzymes :
-
Adenylate cyclase or ATP pyrophosphate-lyase (cyclizing) (EC 4.6.1.1.)
References
Alvarez R, Bruno JJ (1977) Activation of cardiac adenylate cyclase: Hormonal modification of the magnesium ion requirement. Proc Natl Acad Sci USA 74:92–95
Bataille D, Freychet P, Rosselin G (1974) Interactions of glucagon, gut glucagon, vasoactive intestine peptide and secretin with liver and fat cell plasma membranes: Binding to specific sites and stimulation of adenylate cyclase. Endocrinology 95:713–721
Cassel D, Selinger Z (1977) Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Proc Natl Acad Sci USA 74:3307–3311
Chatelain P, Deschodt-Lanckman M, De Neef P, Christophe J, Robberecht P (1979a) Effect of secretin, glucagon and vasoactive intestinal peptide on the hormone-sensitive rat cardiac adenylate cyclase. Arch Int Physiol Biochem 87:783–784
Chatelain P, Robberecht P, De Neef P, Claeys M, Christophe J (1979b) Low responsiveness of cardiac adenylate cyclase activity to peptide hormones in spontaneously hypertensive rats. FEBS Lett 107:486–90
Chiba S (1976) Effect of secretin on pacemaker activity and contractility in the isolated blood-perfused atrium of the dog. Clin Exp Pharmacol Physiol 3:167–172
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 251:4629–4634
De Haën C (1974) Adenylate cyclase. A new kinetic analysis of the effects of hormones and fluoride ion. J Biol Chem 249:2756–2762
Drummond GI, Severson DL, Duncan L (1977) Adenyl cyclase. Kinetic properties and nature of fluoride and hormone stimulation. J Biol Chem 246:4166–4173
Gardner JD, Conlon TP, Beyerman Hc, Van Zon A (1977) Interaction of synthetic 10-tyrosyl analogues of secretin with hormone receptors on pancreatic acinar cells. Gastroenterology 73:52–56
Hannes GG, Rodbell M (1976) Simple model for hormone-activated adenylate cyclase systems. Proc Natl Acad Sci USA 73:1189–1192
Jaeger E, Knof S, Scharf R, Lehnert P, Schulz I, Wünsch E (1978) Chemical evidence for the mechanism of inactivation of secretin. Scand J Gastroenterol 13: Suppl 49:93
Kimura N, Nagata N (1977) The requirement of guanine nucleotides for glucagon stimulation of adenylate cyclase in rat liver plasma membranes. J Biol Chem 252:3829–3835
Kimura N, Nakane K, Nagata N (1976) Activation by GTP of liver adenylate cyclase in the presence of high concentrations of ATP. Biochem Biophys Res Commun 70:1250–1256
Klein I, Levey GS (1971) Activation of myocardial adenyl cyclase by histamine in guinea pig, cat and human heart. J Clin Invest 50:1012–1015
König W, Geiger R, Wissmann H, Bickel M, Obermeier R, Teetz W, Uhmann R (1977a) Chemical and biological properties of porcine secretin and secretin analogues modified in position 3 and 4. Gastroenterology 72:797–800
König W, Bickel M, Geiger R, Obermeier R, Teetz V, Uhmann R, Wissmann H (1977b) Purification and stability of secretin. In: Bonfils S, Fromageot P, Rosselin E (eds) Hormonal receptors in digestive tract physiology. North-Holland Publishing Company, Amsterdam, pp 29–32
König W, Pokorny P, Uhmann R, Teetz V, Wissmann H, Obermeier R, Geiger R (1978) Synthesis of secretin. In: Bloom SR (ed) Gut hormones. Churchill Livingstone, Edinburgh, pp 165–168
König W, Bickel M, Wissmann H, Uhmann R, Geiger R (1979) Secretin analogues. In: Rosselin G, Fromageot P, Bonfils S (eds) Hormone receptors in digestion and nutrition. Elsevier-North Holland Biomedical Press, Amsterdam, pp 137–143
Levitzki A, Helmreich EJM (1979) Hormone-receptor-adenylate cyclase interactions. FEBS Lett 101:213–219
Lin MC, Wright DE, Hruby VJ, Rodbell M (1975) Structure-function relationships in glucagon: Properties of highly purified Des-His1-, monoiodo-, and [Des-Asn28, Thr29] (homoserine lactone27)-glucagon. Biochemistry 14:1559–1563
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent: J Biol Chem 193:265–275
Lundberg JM, Hökfelt T, Kewenter J, Pettersson G, Ahlman H, Edin R, Dahlström A, Nilsson G, Terenius L, Uvnas-Wallensten K, Said S (1979) Substance P-, and enkephalin-like immunoreactivity in the human vagus nerve. Gastroenterology 77:468–471
Mayer SE, Namm DH, Rice L (1970) Effect of glucagon on cyclic 3′, 5′ AMP, phosphorylase activity and contractility of heart muscle of the rat. Circ Res 26:225–233
Murad F, Vaughan M (1969) Effect of glucagon on rat heart adenyl cyclase. Biochem Pharmacol 18:1053–1059
Nickerson M (1973) Adrenergic receptors. Circ Res 32: Suppl 1:53–59
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 251:4635–4639
Robberecht P, De Neef P, Lammens M, Christophe J, König W (1979a) The secretin and VIP receptors of the rat pancreas. Gastroenterol Biol Clin 3:294–295
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 103:229–233
Robberecht P, König W, Deschodt-Lanckman M, De Neef P, Christophe J (1979c) Specificity of receptors to vasoactive intestinal peptide in guinea pig brain. Life Science 25:879–884
Ross G (1970) Cardiovascular effects of secretin. Am J Physiol 18:1166–1170
Said SI, Bosher LP, Spath JA, Kontos HA (1972) Positive inotropic action of newly isolated vasoactive intestinal polypeptide (VIP). Clin Res 20:29
Said SI (1975) Vasoactive intestinal polypeptide (VIP): Current status. In: Thompson JC (ed) Gastrointestinal hormones. University of Texas Press, Austin London, pp 591–597
Salomon Y, Londos C, Rodbell M (1974) A highly sensitive adenylate cyclase assay. Anal Biochem 58:541–548
Snyder FF, Drummond GI (1978) Activation and stabilization of cardiac adenylate cyclase by GTP analog and fluoride. Arch Biochem Biophys 185:116–125
Svoboda M, Robberecht P, Camus J, Deschodt-Lanckman M, Christophe J (1978) Association of binding sites for guanine nucleotides with adenylate cyclase activation in rat pancreatic plasma membranes. Interaction of gastrointestinal hormones. Eur J Biochem 83:287–297
Williams BJ, Mayer SE (1970) Hormonal effects on glycogen metabolism in the rat heart in situ. Mol Pharmacol 2:454–464
Wünsch E, Jaeger E, Moroder L, Schulz I (1977) Progress in the problem of structure activity relations of gastrointestinal hormones. In: Bonfils S, Fromageot P, Rossel in E (eds) Hormonal receptors in digestive tract physiology. North-Holland Publishing Company. Amsterdam, pp 19–27
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chatelain, P., Robberecht, P., De Neef, P. et al. Secretin and VIP-stimulated adenylate cyclase from rat heart. Pflugers Arch. 389, 21–27 (1980). https://doi.org/10.1007/BF00587924
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00587924