Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1981 Aug 1;197(2):459–464. doi: 10.1042/bj1970459

Cyclic nucleotide phosphodiesterase of rat pancreatic islets. Effects of Ca2+, calmodulin and trifluoperazine.

M C Sugden, S J Ashcroft
PMCID: PMC1163146  PMID: 6275834

Abstract

Cyclic nucleotide phosphodiesterase activity towards cyclic AMP and cyclic GMP was studied in extracts of rat islets of Langerhans. Biphasic Eadie plots [Eadie (1942) J. Biol. Chem. 146, 85-93] were obtained with either substrate suggesting the presence of both 'high'- and 'low'-Km components. The apparent Km values were 6.2 +/- 0.5 (n = 8) microM and 103.4 +/- 13.5 (6) microM for cyclic AMP and 3.6 +/- 0.3 (12) microM and 61.4 +/- 7.5 (13) microM for cyclic GMP. With cyclic AMP as substrate, phosphodeisterase activity was increased by calmodulin and Ca2+ and decreased by trifluoperazine, a specific inhibitor of calmodulin. With cyclic GMP as substrate, phosphodiesterase activity was decreased by omission of Ca2+ or addition of trifluoperazine. Addition of exogenous calmodulin had no effect on activity. The data suggest that Ca2+ may influence the islet content of cyclic AMP and cyclic GMP via effects on calmodulin-dependent cyclic nucleotide phosphodiesterase(s).

Full text

PDF
459

Selected References

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

  1. Ashcroft S. J. Glucoreceptor mechanisms and the control of insulin release and biosynthesis. Diabetologia. 1980 Jan;18(1):5–15. doi: 10.1007/BF01228295. [DOI] [PubMed] [Google Scholar]
  2. Ashcroft S. J.H., Randle P. J., Täljedal I. -B. Cyclic nucleotide phosphodiesterase activity in normal mouse pancreatic islets. FEBS Lett. 1972 Feb 15;20(3):263–266. doi: 10.1016/0014-5793(72)80082-6. [DOI] [PubMed] [Google Scholar]
  3. Brostrom C. O., Huang Y. C., Breckenridge B. M., Wolff D. J. Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase. Proc Natl Acad Sci U S A. 1975 Jan;72(1):64–68. doi: 10.1073/pnas.72.1.64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Capito K., Hedeskov C. J. The effect of starvation on phosphodiesterase activity and the content of adenosine 3' :5'-cyclic monophosphate in isolated mouse pancreatic islets. Biochem J. 1974 Sep;142(3):653–658. doi: 10.1042/bj1420653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Charles M. A., Lawecki J., Steiner A. L., Grodsky G. M. Cyclic nucleotides in pancreatic islets. Tolbutamide- and arginine-induced insulin release. Diabetes. 1976 Apr;25(4):256–259. doi: 10.2337/diab.25.4.256. [DOI] [PubMed] [Google Scholar]
  6. Cheung W. Y. Cyclic 3',5'-nucleotide phosphodiesterase. Demonstration of an activator. Biochem Biophys Res Commun. 1970 Feb 6;38(3):533–538. doi: 10.1016/0006-291x(70)90747-3. [DOI] [PubMed] [Google Scholar]
  7. Cohen P., Burchell A., Foulkes J. G., Cohen P. T., Vanaman T. C., Nairn C. Identification of the Ca2+-dependent modulator protein as the fourth subunit of rabbit skeletal muscle phosphorylase kinase. FEBS Lett. 1978 Aug 15;92(2):287–293. doi: 10.1016/0014-5793(78)80772-8. [DOI] [PubMed] [Google Scholar]
  8. Coll-Garcia E., Gill J. R. Insulin release by isolated pancreatic islets of the mouse incubated in vitro. Diabetologia. 1969 Apr;5(2):61–66. doi: 10.1007/BF01211999. [DOI] [PubMed] [Google Scholar]
  9. Gagerman E., Hellman B. Islet contents of cyclic 3',5'-guanosine monophosphate under conditions which affect the cyclic 3',5'-adenosine monophosphate. Acta Endocrinol (Copenh) 1977 Oct;86(2):344–354. doi: 10.1530/acta.0.0860344. [DOI] [PubMed] [Google Scholar]
  10. Gagerman E., Idahl L. A., Meissner H. P., Täljedal I. B. Insulin release, cGMP, cAMP, and membrane potential in acetylcholine-stimulated islets. Am J Physiol. 1978 Nov;235(5):E493–E500. doi: 10.1152/ajpendo.1978.235.5.E493. [DOI] [PubMed] [Google Scholar]
  11. Gagliardino J. J., Harrison D. E., Christie M. R., Gagliardino E. E., Ashcroft S. J. Evidence for the participation of calmodulin in stimulus-secretion coupling in the pancreatic beta-cell. Biochem J. 1980 Dec 15;192(3):919–927. doi: 10.1042/bj1920919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Howell S. L., Montague W. Regulation of guanylate cyclase in guinea-pig islets of Langerhans. Biochem J. 1974 Aug;142(2):379–384. doi: 10.1042/bj1420379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Levin R. M., Weiss B. Binding of trifluoperazine to the calcium-dependent activator of cyclic nucleotide phosphodiesterase. Mol Pharmacol. 1977 Jul;13(4):690–697. [PubMed] [Google Scholar]
  14. Sams D. J., Montague W. The role of adenosine 3':5'-cyclic monophosphate in the regulation of insulin release. Properties of islet-cell adenosine 3':5'-cyclic monophosphate phosphodiesterase. Biochem J. 1972 Oct;129(4):945–952. doi: 10.1042/bj1290945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sharp G. W. The adenylate cyclase-cyclic AMP system in islets of Langerhans and its role in the control of insulin release. Diabetologia. 1979 May;16(5):287–296. doi: 10.1007/BF01223617. [DOI] [PubMed] [Google Scholar]
  16. Sugden M. C., Christie M. R., Ashcroft S. J. Presence and possible role of calcium-dependent regulator (calmodulin) in rat islets of Langerhans. FEBS Lett. 1979 Sep 1;105(1):95–100. doi: 10.1016/0014-5793(79)80894-7. [DOI] [PubMed] [Google Scholar]
  17. Valverde I., Vandermeers A., Anjaneyulu R., Malaisse W. J. Calmodulin activation of adenylate cyclase in pancreatic islets. Science. 1979 Oct 12;206(4415):225–227. doi: 10.1126/science.225798. [DOI] [PubMed] [Google Scholar]
  18. Zawalich W. S., Karl R. C., Ferrendelli J. A., Matschinsky F. M. Factors governing glucose induced elevation of cyclic 3'5' AMP levels in pancreatic islets. Diabetologia. 1975 Jun;11(3):231–235. doi: 10.1007/BF00422327. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES