Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1984 Dec;83(4):927–933. doi: 10.1111/j.1476-5381.1984.tb16533.x

Effects of adenosine, adenosine triphosphate and structural analogues on glucagon secretion from the perfused pancreas of rat in vitro.

J Chapal, M M Loubatières-Mariani, M Roye, A Zerbib
PMCID: PMC1986985  PMID: 6097328

Abstract

The effects of adenosine, adenosine triphosphate (ATP) and structural analogues have been studied on glucagon secretion from the isolated perfused pancreas of the rat in the presence of glucose (2.8 mM). Adenosine induced a transient increase of glucagon secretion. This effect was concentration-dependent in the range of 0.165 to 165 microM. ATP also induced an increase, but the effect was no greater at 165 microM than at 16.5 microM. 2-Chloroadenosine, an analogue more resistant to metabolism or uptake systems than adenosine, was more effective. Among the three structural analogues of ATP or ADP studied, beta, gamma-methylene ATP which can be hydrolyzed into AMP and adenosine had an effect similar to adenosine or ATP at the same concentrations (1.65 and 16.5 microM); in contrast alpha, beta-methylene ATP and alpha, beta-methylene ADP (resistant to hydrolysis into AMP and adenosine) were ineffective. Theophylline (50 microM) a specific blocker of the adenosine receptor, suppressed the glucagon peak induced by adenosine, 2-chloroadenosine, ATP and beta, gamma-methylene ATP (1.65 microM). An inhibitor of 5' nucleotidase, alpha, beta-methylene ADP (16.5 microM), reduced the glucagon increase induced by ATP and did not affect the response to adenosine (1.65 microM). These results support the hypothesis of adenosine receptors (P1-purinoceptors) on the pancreatic glucagon secretory cells and indicate that ATP acts after hydrolysis to adenosine.

Full text

PDF
927

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bacher S., Kraupp O., Conca W., Raberger G. The effects of NECA (adenosine-5'N-ethylcarboxamide) and of adenosine on glucagon and insulin release from the in situ isolated blood-perfused pancreas in anesthetized dogs. Naunyn Schmiedebergs Arch Pharmacol. 1982 Jul;320(1):67–71. doi: 10.1007/BF00499075. [DOI] [PubMed] [Google Scholar]
  2. Brown C. M., Burnstock G. Evidence in support of the P1/P2 purinoceptor hypothesis in the guinea-pig taenia coli. Br J Pharmacol. 1981 Jul;73(3):617–624. doi: 10.1111/j.1476-5381.1981.tb16796.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burger R. M., Lowenstein J. M. Preparation and properties of 5'-nucleotidase from smooth muscle of small intestine. J Biol Chem. 1970 Dec 10;245(23):6274–6280. [PubMed] [Google Scholar]
  4. CLARKE D. A., DAVOLL J., PHILIPS F. S., BROWN G. B. Enzymatic deamination and vasodepressor effects of adenosine analogs. J Pharmacol Exp Ther. 1952 Nov;106(3):291–302. [PubMed] [Google Scholar]
  5. Chapal J., Loubatieres-Mariani M. M. Attempt to antagonized the stimulatory effect or ATP on insulin secretion. Eur J Pharmacol. 1981 Sep 11;74(2-3):127–134. doi: 10.1016/0014-2999(81)90522-7. [DOI] [PubMed] [Google Scholar]
  6. Christie J., Satchell D. G. Purine receptors in the trachea: is there a receptor for ATP? Br J Pharmacol. 1980 Dec;70(4):512–514. doi: 10.1111/j.1476-5381.1980.tb09768.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Daly J. W. Adenosine receptors: targets for future drugs. J Med Chem. 1982 Mar;25(3):197–207. doi: 10.1021/jm00345a001. [DOI] [PubMed] [Google Scholar]
  8. Flodgaard H., Torp-Pedersen C. A calcium ion-dependent adenosine triphosphate pyrophosphohydrolase in plasma membrane from rat liver. Demonstration that the adenosine triphosphate analogues adenosine 5'-[betagamma-imido]triphosphate and adenosine 5'-[betagamma-methylene]-triphosphate are substrates for the enzyme. Biochem J. 1978 Jun 1;171(3):817–820. doi: 10.1042/bj1710817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lernmark A., Nathans A., Steiner D. F. Preparation and characterization of plasma membrane-enriched fractions from rat pancreatic islets. J Cell Biol. 1976 Nov;71(2):606–623. doi: 10.1083/jcb.71.2.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Levin S. R., Kasson B. G., Driessen J. F. Adenosine triphosphatases of rat pancreatic islets: comparison with those of rat kidney. J Clin Invest. 1978 Sep;62(3):692–701. doi: 10.1172/JCI109177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Loubatieres-Mariani M. M., Chapal J., Lignon F., Valette G. Structural specificity of nucleotides for insulin secretory action from the isolated perfused rat pancreas. Eur J Pharmacol. 1979 Nov 16;59(3-4):277–286. doi: 10.1016/0014-2999(79)90291-7. [DOI] [PubMed] [Google Scholar]
  12. Loubatières-Mariani M. M., Chapal J., Roye M. Effets de l'adénosine sur les sécrétions de glucagon et d'insuline du pancréas isolé et perfusé du rat. C R Seances Soc Biol Fil. 1982;176(5):663–669. [PubMed] [Google Scholar]
  13. Loubatières-Mariani M. M., Loubatières A. L., Chapal J., Valette G. Adénosine triphosphate (ATP) et glucose. Action sur les sécrétions d'insuline et de glucagon. C R Seances Soc Biol Fil. 1976;170(4):833–836. [PubMed] [Google Scholar]
  14. Loubatières A., Mariani M. M., Ribes G., de Malbosc H., Chapal J. Etude expérimentale d'un nouveau sulfamide hypoglycémiant particulièrement actif, le HB 419 ou glibenclamide. Diabetologia. 1969 Feb;5(1):1–10. doi: 10.1007/BF01212212. [DOI] [PubMed] [Google Scholar]
  15. McQueen D. S., Ribeiro J. A. On the specificity and type of receptor involved in carotid body chemoreceptor activation by adenosine in the cat. Br J Pharmacol. 1983 Oct;80(2):347–354. doi: 10.1111/j.1476-5381.1983.tb10040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muller M. J., Paton D. M. Presynaptic inhibitory actions of 2-substituted adenosine derivatives on neurotransmission in rat vas deferens: effects of inhibitors of adenosine uptake and deamination. Naunyn Schmiedebergs Arch Pharmacol. 1979 Jan;306(1):23–28. doi: 10.1007/BF00515589. [DOI] [PubMed] [Google Scholar]
  17. Okwuasaba F. K., Hamilton J. T., Cook M. A. Relaxations of guinea-pig fundic strip by adenosine, adenine nucleotides and electrical stimulation: antagonsism by theophylline and desensitization to adenosine and its derivatives. Eur J Pharmacol. 1977 Dec 1;46(3):181–198. doi: 10.1016/0014-2999(77)90333-8. [DOI] [PubMed] [Google Scholar]
  18. Petrack B., Czernik A. J., Ansell J., Cassidy J. Potentiation of arginine-induced glucagon secretion by adenosine. Life Sci. 1981 Jun 8;28(23):2611–2615. doi: 10.1016/0024-3205(81)90718-9. [DOI] [PubMed] [Google Scholar]
  19. Phillis J. W., Edstrom J. P. Effects of adenosine analogs on rat cerebral cortical neurons. Life Sci. 1976 Oct 1;19(7):1041–1053. doi: 10.1016/0024-3205(76)90296-4. [DOI] [PubMed] [Google Scholar]
  20. Unger R. H., Aguilar-Parada E., Müller W. A., Eisentraut A. M. Studies of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest. 1970 Apr;49(4):837–848. doi: 10.1172/JCI106297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Weir G. C., Knowlton S. D., Martin D. B. Nucleotide and nucleoside stimulation of glucagon secretion. Endocrinology. 1975 Oct;97(4):932–936. doi: 10.1210/endo-97-4-932. [DOI] [PubMed] [Google Scholar]
  22. Yount R. G. ATP analogs. Adv Enzymol Relat Areas Mol Biol. 1975;43:1–56. doi: 10.1002/9780470122884.ch1. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES