Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1986 Apr 1;235(1):145–149. doi: 10.1042/bj2350145

The action of islet activating protein (pertussis toxin) on insulin's ability to inhibit adenylate cyclase and activate cyclic AMP phosphodiesterases in hepatocytes.

C M Heyworth, A M Grey, S R Wilson, E Hanski, M D Houslay
PMCID: PMC1146661  PMID: 3017298

Abstract

Treatment of hepatocytes with islet activating protein (pertussis toxin) from Bordetella pertussis blocked the ability of insulin to inhibit adenylate cyclase activity both in broken plasma membranes and in intact hepatocytes. Such treatment of intact hepatocytes with pertussis toxin did not prevent insulin from activating the peripheral plasma membrane cyclic AMP phosphodiesterase although it did inhibit the ability of insulin to activate the 'dense-vesicle' cyclic AMP phosphodiesterase. The ability of glucagon pretreatment of hepatocytes to block insulin's activation of the plasma membrane cyclic AMP phosphodiesterase was abolished in pertussis toxin-treated hepatocytes. It is suggested that the ability of insulin to manipulate cyclic AMP concentrations by inhibiting adenylate cyclase and activating the plasma membrane and 'dense-vesicle' cyclic AMP phosphodiesterases involves interactions with the guanine nucleotide regulatory protein system occurring in liver plasma membranes.

Full text

PDF
145

Selected References

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

  1. Bokoch G. M., Katada T., Northup J. K., Hewlett E. L., Gilman A. G. Identification of the predominant substrate for ADP-ribosylation by islet activating protein. J Biol Chem. 1983 Feb 25;258(4):2072–2075. [PubMed] [Google Scholar]
  2. Codina J., Hildebrandt J. D., Sekura R. D., Birnbaumer M., Bryan J., Manclark C. R., Iyengar R., Birnbaumer L. Ns and Ni, the stimulatory and inhibitory regulatory components of adenylyl cyclases. Purification of the human erythrocyte proteins without the use of activating regulatory ligands. J Biol Chem. 1984 May 10;259(9):5871–5886. [PubMed] [Google Scholar]
  3. Codina J., Hildebrandt J., Iyengar R., Birnbaumer L., Sekura R. D., Manclark C. R. Pertussis toxin substrate, the putative Ni component of adenylyl cyclases, is an alpha beta heterodimer regulated by guanine nucleotide and magnesium. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4276–4280. doi: 10.1073/pnas.80.14.4276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elks M. L., Watkins P. A., Manganiello V. C., Moss J., Hewlett E., Vaughan M. Selective regulation by pertussis toxin of insulin-induced activation of particulate cAMP phosphodiesterase activity in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 1983 Oct 31;116(2):593–598. doi: 10.1016/0006-291x(83)90565-x. [DOI] [PubMed] [Google Scholar]
  5. Gilman A. G. G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577–579. doi: 10.1016/0092-8674(84)90336-2. [DOI] [PubMed] [Google Scholar]
  6. Hanski E., Gilman A. G. The guanine nucleotide-binding regulatory component of adenylate cyclase in human erythrocytes. J Cyclic Nucleotide Res. 1982;8(5):323–336. [PubMed] [Google Scholar]
  7. Hazeki O., Ui M. Modification by islet-activating protein of receptor-mediated regulation of cyclic AMP accumulation in isolated rat heart cells. J Biol Chem. 1981 Mar 25;256(6):2856–2862. [PubMed] [Google Scholar]
  8. Heyworth C. M., Hanski E., Houslay M. D. Islet-activating protein blocks glucagon desensitization in intact hepatocytes. Biochem J. 1984 Aug 15;222(1):189–194. doi: 10.1042/bj2220189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Heyworth C. M., Houslay M. D. Challenge of hepatocytes by glucagon triggers a rapid modulation of adenylate cyclase activity in isolated membranes. Biochem J. 1983 Jul 15;214(1):93–98. doi: 10.1042/bj2140093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heyworth C. M., Houslay M. D. Insulin exerts actions through a distinct species of guanine nucleotide regulatory protein: inhibition of adenylate cyclase. Biochem J. 1983 Aug 15;214(2):547–552. doi: 10.1042/bj2140547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heyworth C. M., Rawal S., Houslay M. D. Guanine nucleotides can activate the insulin-stimulated phosphodiesterase in liver plasma membranes. FEBS Lett. 1983 Apr 5;154(1):87–91. doi: 10.1016/0014-5793(83)80880-1. [DOI] [PubMed] [Google Scholar]
  12. Heyworth C. M., Wallace A. V., Houslay M. D. Insulin and glucagon regulate the activation of two distinct membrane-bound cyclic AMP phosphodiesterases in hepatocytes. Biochem J. 1983 Jul 15;214(1):99–110. doi: 10.1042/bj2140099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heyworth C. M., Wallace A. V., Wilson S. R., Houslay M. D. An assessment of the ability of insulin-stimulated cyclic AMP phosphodiesterase to decrease hepatocyte intracellular cyclic AMP concentrations. Biochem J. 1984 Aug 15;222(1):183–187. doi: 10.1042/bj2220183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heyworth C. M., Whetton A. D., Wong S., Martin B. R., Houslay M. D. Insulin inhibits the cholera-toxin-catalysed ribosylation of a Mr-25000 protein in rat liver plasma membranes. Biochem J. 1985 Jun 15;228(3):593–603. doi: 10.1042/bj2280593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heyworth C. M., Wilson S. P., Gawler D. J., Houslay M. D. The phorbol ester TPA prevents the expression of both glucagon desensitisation and the glucagon-mediated block of insulin stimulation of the peripheral plasma membrane cyclic AMP phosphodiesterase in rat hepatocytes. FEBS Lett. 1985 Aug 5;187(2):196–200. doi: 10.1016/0014-5793(85)81241-2. [DOI] [PubMed] [Google Scholar]
  16. Hildebrandt J. D., Hanoune J., Birnbaumer L. Guanine nucleotide inhibition of cyc- S49 mouse lymphoma cell membrane adenylyl cyclase. J Biol Chem. 1982 Dec 25;257(24):14723–14725. [PubMed] [Google Scholar]
  17. Hildebrandt J. D., Sekura R. D., Codina J., Iyengar R., Manclark C. R., Birnbaumer L. Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins. Nature. 1983 Apr 21;302(5910):706–709. doi: 10.1038/302706a0. [DOI] [PubMed] [Google Scholar]
  18. Houslay M. D., Elliott K. R. Cholera toxin mediated activation of adenylate cyclase in intact rat hepatocytes. FEBS Lett. 1979 Aug 15;104(2):359–363. doi: 10.1016/0014-5793(79)80852-2. [DOI] [PubMed] [Google Scholar]
  19. Houslay M. D., Elliott K. R. Is the receptor-mediated endocytosis of cholera toxin A pre-requisite for its activation of adenylate cyclase in intact rat hepatocytes? FEBS Lett. 1981 Jun 15;128(2):289–292. doi: 10.1016/0014-5793(81)80101-9. [DOI] [PubMed] [Google Scholar]
  20. Itoh H., Okajima F., Ui M. Conversion of adrenergic mechanism from an alpha- to a beta-type during primary culture of rat hepatocytes. Accompanying decreases in the function of the inhibitory guanine nucleotide regulatory component of adenylate cyclase identified as the substrate of islet-activating protein. J Biol Chem. 1984 Dec 25;259(24):15464–15473. [PubMed] [Google Scholar]
  21. Jakobs K. H., Schultz G. Occurrence of a hormone-sensitive inhibitory coupling component of the adenylate cyclase in S49 lymphoma cyc- variants. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3899–3902. doi: 10.1073/pnas.80.13.3899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Katada T., Amano T., Ui M. Modulation by islet-activating protein of adenylate cyclase activity in C6 glioma cells. J Biol Chem. 1982 Apr 10;257(7):3739–3746. [PubMed] [Google Scholar]
  23. Katada T., Ui M. Islet-activating protein. A modifier of receptor-mediated regulation of rat islet adenylate cyclase. J Biol Chem. 1981 Aug 25;256(16):8310–8317. [PubMed] [Google Scholar]
  24. Katada T., Ui M. Islet-activating protein. Enhanced insulin secretion and cyclic AMP accumulation in pancreatic islets due to activation of native calcium ionophores. J Biol Chem. 1979 Jan 25;254(2):469–479. [PubMed] [Google Scholar]
  25. Katada T., Ui M. Slow interaction of islet-activating protein with pancreatic islets during primary culture to cause reversal of alpha-adrenergic inhibition of insulin secretion. J Biol Chem. 1980 Oct 25;255(20):9580–9588. [PubMed] [Google Scholar]
  26. Kurose H., Katada T., Amano T., Ui M. Specific uncoupling by islet-activating protein, pertussis toxin, of negative signal transduction via alpha-adrenergic, cholinergic, and opiate receptors in neuroblastoma x glioma hybrid cells. J Biol Chem. 1983 Apr 25;258(8):4870–4875. [PubMed] [Google Scholar]
  27. Manning D. R., Gilman A. G. The regulatory components of adenylate cyclase and transducin. A family of structurally homologous guanine nucleotide-binding proteins. J Biol Chem. 1983 Jun 10;258(11):7059–7063. [PubMed] [Google Scholar]
  28. Murayama T., Katada T., Ui M. Guanine nucleotide activation and inhibition of adenylate cyclase as modified by islet-activating protein, pertussis toxin, in mouse 3T3 fibroblasts. Arch Biochem Biophys. 1983 Mar;221(2):381–390. doi: 10.1016/0003-9861(83)90157-1. [DOI] [PubMed] [Google Scholar]
  29. Nakamura T., Ui M. Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca2+-mobilizing receptor-mediated biosignaling system. J Biol Chem. 1985 Mar 25;260(6):3584–3593. [PubMed] [Google Scholar]
  30. Rich K. A., Codina J., Floyd G., Sekura R., Hildebrandt J. D., Iyengar R. Glucagon-induced heterologous desensitization of the MDCK cell adenylyl cyclase. Increases in the apparent levels of the inhibitory regulator (Ni). J Biol Chem. 1984 Jun 25;259(12):7893–7901. [PubMed] [Google Scholar]
  31. Rubin C. S., Erlichman J., Rosen O. M. Cyclic AMP-dependent protein kinase from bovine heart muscle. Methods Enzymol. 1974;38:308–315. doi: 10.1016/0076-6879(74)38047-0. [DOI] [PubMed] [Google Scholar]
  32. Salomon Y., Londos C., Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem. 1974 Apr;58(2):541–548. doi: 10.1016/0003-2697(74)90222-x. [DOI] [PubMed] [Google Scholar]
  33. Sternweis P. C., Robishaw J. D. Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J Biol Chem. 1984 Nov 25;259(22):13806–13813. [PubMed] [Google Scholar]
  34. Wallace A. V., Heyworth C. M., Houslay M. D. N6-(Phenylisopropyl)adenosine prevents glucagon both blocking insulin's activation of the plasma-membrane cyclic AMP phosphodiesterase and uncoupling hormonal stimulation of adenylate cyclase activity in hepatocytes. Biochem J. 1984 Aug 15;222(1):177–182. doi: 10.1042/bj2220177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Whetton A. D., Needham L., Dodd N. J., Heyworth C. M., Houslay M. D. Forskolin and ethanol both perturb the structure of liver plasma membranes and activate adenylate cyclase activity. Biochem Pharmacol. 1983 May 15;32(10):1601–1608. doi: 10.1016/0006-2952(83)90334-9. [DOI] [PubMed] [Google Scholar]
  36. Wilson S. R., Wallace A. V., Houslay M. D. Insulin activates the plasma-membrane and dense-vesicle cyclic AMP phosphodiesterase in hepatocytes by distinct routes. Biochem J. 1983 Oct 15;216(1):245–248. doi: 10.1042/bj2160245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yajima M., Hosoda K., Kanbayashi Y., Nakamura T., Takahashi I., Ui M. Biological properties of islets-activating protein (IAP) purified from the culture medium of Bordetella pertussis. J Biochem. 1978 Jan;83(1):305–312. doi: 10.1093/oxfordjournals.jbchem.a131905. [DOI] [PubMed] [Google Scholar]

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

RESOURCES