Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1986 Aug 15;238(1):109–113. doi: 10.1042/bj2380109

Thrombin, unlike vasopressin, appears to stimulate two distinct guanine nucleotide regulatory proteins in human platelets.

M D Houslay, D Bojanic, D Gawler, S O'Hagan, A Wilson
PMCID: PMC1147103  PMID: 3099763

Abstract

The thrombin-stimulated GTPase activity of human platelets was additive with respect to the GTPase stimulation effected by prostaglandin E1, but not with that stimulated by adrenaline, vasopressin and platelet-activating factor (PAF). Treatment of platelet membranes with pertussis toxin partially inhibited the thrombin-stimulated GTPase, but had no effect on the vasopressin-stimulated GTPase activity, whereas cholera toxin treatment had no effect on either of these stimulated GTPase activities. Thrombin, adrenaline and PAF, but not vasopressin, inhibited the adenylate cyclase activity of isolated plasma membranes through the action of Ni only, this being inhibited by pertussis toxin. It is suggested that thrombin exerts effects through both the inhibitory guanine nucleotide regulatory protein Ni and through the putative guanine nucleotide regulatory protein, Np, involved in regulating receptor-stimulated inositol phospholipid metabolism. However, vasopressin appears to exert its effects solely through the putative Np.

Full text

PDF

Selected References

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

  1. Agranoff B. W., Murthy P., Seguin E. B. Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets. J Biol Chem. 1983 Feb 25;258(4):2076–2078. [PubMed] [Google Scholar]
  2. Aktories K., Jakobs K. H. Ni-mediated inhibition of human platelet adenylate cyclase by thrombin. Eur J Biochem. 1984 Dec 3;145(2):333–338. doi: 10.1111/j.1432-1033.1984.tb08558.x. [DOI] [PubMed] [Google Scholar]
  3. Aktories K., Schultz G., Jakobs K. H. Cholera toxin does not impair hormonal inhibition of adenylate cyclase and concomitant stimulation of a GTPase in adipocyte membranes. Biochim Biophys Acta. 1982 Oct 28;719(1):58–64. doi: 10.1016/0304-4165(82)90307-5. [DOI] [PubMed] [Google Scholar]
  4. Bell R. L., Majerus P. W. Thrombin-induced hydrolysis of phosphatidylinositol in human platelets. J Biol Chem. 1980 Mar 10;255(5):1790–1792. [PubMed] [Google Scholar]
  5. Billah M. M., Lapetina E. G. Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets. J Biol Chem. 1982 Nov 10;257(21):12705–12708. [PubMed] [Google Scholar]
  6. Cassel D., Selinger Z. Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes. Biochim Biophys Acta. 1976 Dec 8;452(2):538–551. doi: 10.1016/0005-2744(76)90206-0. [DOI] [PubMed] [Google Scholar]
  7. Cockcroft S., Gomperts B. D. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature. 1985 Apr 11;314(6011):534–536. doi: 10.1038/314534a0. [DOI] [PubMed] [Google Scholar]
  8. Fain J. N., Brindley D. N., Pittner R. A., Hawthorne J. N. Stimulation of specific GTPase activity by vasopressin in isolated membranes from cultured rat hepatocytes. FEBS Lett. 1985 Nov 18;192(2):251–254. doi: 10.1016/0014-5793(85)80118-6. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Gomperts B. D. Involvement of guanine nucleotide-binding protein in the gating of Ca2+ by receptors. Nature. 1983 Nov 3;306(5938):64–66. doi: 10.1038/306064a0. [DOI] [PubMed] [Google Scholar]
  11. Haslam R. J., Davidson M. M. Guanine nucleotides decrease the free [Ca2+] required for secretion of serotonin from permeabilized blood platelets. Evidence of a role for a GTP-binding protein in platelet activation. FEBS Lett. 1984 Aug 20;174(1):90–95. doi: 10.1016/0014-5793(84)81084-4. [DOI] [PubMed] [Google Scholar]
  12. Haslam R. J., Vanderwel M. Inhibition of platelet adenylate cyclase by 1-O-alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (platelet-activating factor). J Biol Chem. 1982 Jun 25;257(12):6879–6885. [PubMed] [Google Scholar]
  13. Heyworth C. M., Whetton A. D., Kinsella A. R., Houslay M. D. The phorbol ester, TPA inhibits glucagon-stimulated adenylate cyclase activity. FEBS Lett. 1984 May 7;170(1):38–42. doi: 10.1016/0014-5793(84)81364-2. [DOI] [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. 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]
  16. Houslay M. D., Bojanic D., Wilson A. Platelet activating factor and U44069 stimulate a GTPase activity in human platelets which is distinct from the guanine nucleotide regulatory proteins, Ns and Ni. Biochem J. 1986 Mar 15;234(3):737–740. doi: 10.1042/bj2340737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Houslay M. D., Metcalfe J. C., Warren G. B., Hesketh T. R., Smith G. A. The glucagon receptor of rat liver plasma membrane can couple to adenylate cyclase without activating it. Biochim Biophys Acta. 1976 Jun 17;436(2):489–494. doi: 10.1016/0005-2736(76)90210-8. [DOI] [PubMed] [Google Scholar]
  18. Jakobs K. H., Aktories K., Minuth M., Schultz G. Inhibition of adenylate cyclase. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1985;19:137–150. [PubMed] [Google Scholar]
  19. Jakobs K. H., Lasch P., Minuth M., Aktories K., Schultz G. Uncoupling of alpha-adrenoceptor-mediated inhibition of human platelet adenylate cyclase by N-ethylmaleimide. J Biol Chem. 1982 Mar 25;257(6):2829–2833. [PubMed] [Google Scholar]
  20. Jard S., Cantau B., Jakobs K. H. Angiotensin II and alpha-adrenergic agonists inhibit rat liver adenylate cyclase. J Biol Chem. 1981 Mar 25;256(6):2603–2606. [PubMed] [Google Scholar]
  21. Lenox R. H., Ellis J., Van Riper D., Ehrlich Y. H. Alpha 2-adrenergic receptor-mediated regulation of adenylate cyclase in the intact human platelet. Evidence for a receptor reserve. Mol Pharmacol. 1985 Jan;27(1):1–9. [PubMed] [Google Scholar]
  22. Lester H. A., Steer M. L., Levitzki A. Prostaglandin-stimulated GTP hydrolysis associated with activation of adenylate cyclase in human platelet membranes. Proc Natl Acad Sci U S A. 1982 Feb;79(3):719–723. doi: 10.1073/pnas.79.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Limbird L. E. Activation and attenuation of adenylate cyclase. The role of GTP-binding proteins as macromolecular messengers in receptor--cyclase coupling. Biochem J. 1981 Apr 1;195(1):1–13. doi: 10.1042/bj1950001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Litosch I., Wallis C., Fain J. N. 5-Hydroxytryptamine stimulates inositol phosphate production in a cell-free system from blowfly salivary glands. Evidence for a role of GTP in coupling receptor activation to phosphoinositide breakdown. J Biol Chem. 1985 May 10;260(9):5464–5471. [PubMed] [Google Scholar]
  25. MacIntyre D. E., Pollock W. K. Platelet-activating factor stimulates phosphatidylinositol turnover in human platelets. Biochem J. 1983 May 15;212(2):433–437. doi: 10.1042/bj2120433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McGowan E. B., Detwiler T. C. Modified platelet responses to thrombin. Evidence for two types of receptors or coupling mechanisms. J Biol Chem. 1986 Jan 15;261(2):739–746. [PubMed] [Google Scholar]
  27. Michell R. H., Kirk C. J., Billah M. M. Hormonal stimulation of phosphatidylinositol breakdown with particular reference to the hepatic effects of vasopressin. Biochem Soc Trans. 1979 Oct;7(5):861–865. doi: 10.1042/bst0070861. [DOI] [PubMed] [Google Scholar]
  28. Pollock W. K., Armstrong R. A., Brydon L. J., Jones R. L., MacIntyre D. E. Thromboxane-induced phosphatidate formation in human platelets. Relationship to receptor occupancy and to changes in cytosolic free calcium. Biochem J. 1984 May 1;219(3):833–842. doi: 10.1042/bj2190833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pollock W. K., MacIntyre D. E. Desensitization and antagonism of vasopressin-induced phosphoinositide metabolism and elevation of cytosolic free calcium concentration in human platelets. Biochem J. 1986 Feb 15;234(1):67–73. doi: 10.1042/bj2340067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sawyer W. H., Grzonka Z., Manning M. Neurohypophysial peptides. Design of tissue-specific agonists and antagonists. Mol Cell Endocrinol. 1981 May;22(2):117–134. doi: 10.1016/0303-7207(81)90086-1. [DOI] [PubMed] [Google Scholar]
  31. Seamon K. B., Daly J. W. Forskolin: a unique diterpene activator of cyclic AMP-generating systems. J Cyclic Nucleotide Res. 1981;7(4):201–224. [PubMed] [Google Scholar]
  32. Siess W., Stifel M., Binder H., Weber P. C. Activation of V1-receptors by vasopressin stimulates inositol phospholipid hydrolysis and arachidonate metabolism in human platelets. Biochem J. 1986 Jan 1;233(1):83–91. doi: 10.1042/bj2330083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vanderwel M., Lum D. S., Haslam R. J. Vasopressin inhibits the adenylate cyclase activity of human platelet particulate fraction through V1-receptors. FEBS Lett. 1983 Dec 12;164(2):340–344. doi: 10.1016/0014-5793(83)80313-5. [DOI] [PubMed] [Google Scholar]
  34. 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]

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

RESOURCES