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. 1987 Dec;394:239–248. doi: 10.1113/jphysiol.1987.sp016868

Protein kinase C activators inhibit the inositol trisphosphate-mediated muscarinic current responses in rat lacrimal cells.

I Llano 1, A Marty 1
PMCID: PMC1191959  PMID: 3327945

Abstract

1. Pre-incubation (1-5 min) with 12-O-tetradecanoylphorbol-13-acetate (TPA, 8-16 nM), a tumour-promoting phorbol ester known to activate protein kinase C, was found to inhibit acetylcholine-induced Ca2+-dependent K+ and Cl- currents in cells isolated from rat lacrimal glands. 2. Previous work showed that the same currents may be elicited by dialysing cells with a high-Ca2+ (1.0 microM) solution, with inositol trisphosphate (InsP3), or with guanosine 5'-[gamma-thio]triphosphate (GTP-gamma-S). 3. After TPA incubation both types of currents could be elicited by dialysis with elevated Ca2+ solutions, although the magnitude of the K+ current was slightly reduced in comparison with control cells. 4. Responses to intracellular dialysis with InsP3 (20 microM) were similar to those in untreated cells, indicating that the Ca2+ release process was unaffected. 5. However, the response to GTP-gamma-S (0.2-0.5 mM) dialysis was strongly inhibited in TPA-treated cells. 6. These results suggest that protein kinase C exerts an inhibitory action on the pathway leading from receptor activation to inositol trisphosphate production.

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Selected References

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

  1. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  2. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  3. 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]
  4. Drummond A. H. Inositol lipid metabolism and signal transduction in clonal pituitary cells. J Exp Biol. 1986 Sep;124:337–358. doi: 10.1242/jeb.124.1.337. [DOI] [PubMed] [Google Scholar]
  5. Evans M. G., Marty A. Calcium-dependent chloride currents in isolated cells from rat lacrimal glands. J Physiol. 1986 Sep;378:437–460. doi: 10.1113/jphysiol.1986.sp016229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans M. G., Marty A. Potentiation of muscarinic and alpha-adrenergic responses by an analogue of guanosine 5'-triphosphate. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4099–4103. doi: 10.1073/pnas.83.11.4099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  8. Kanba S., Kanba K. S., Richelson E. The protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibits muscarinic (M1) receptor-mediated inositol phosphate release and cyclic GMP formation in murine neuroblastoma cells (clone N1E-115). Eur J Pharmacol. 1986 Jun 5;125(1):155–156. doi: 10.1016/0014-2999(86)90096-8. [DOI] [PubMed] [Google Scholar]
  9. Katada T., Gilman A. G., Watanabe Y., Bauer S., Jakobs K. H. Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem. 1985 Sep 2;151(2):431–437. doi: 10.1111/j.1432-1033.1985.tb09120.x. [DOI] [PubMed] [Google Scholar]
  10. Krishtal O. A., Pidoplichko V. I. A receptor for protons in the nerve cell membrane. Neuroscience. 1980;5(12):2325–2327. doi: 10.1016/0306-4522(80)90149-9. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Llano I., Marty A., Tanguy J. Dependence of intracellular effects of GTP gamma S and inositoltrisphosphate on cell membrane potential and on external Ca ions. Pflugers Arch. 1987 Aug;409(4-5):499–506. doi: 10.1007/BF00583807. [DOI] [PubMed] [Google Scholar]
  13. Malenka R. C., Madison D. V., Andrade R., Nicoll R. A. Phorbol esters mimic some cholinergic actions in hippocampal pyramidal neurons. J Neurosci. 1986 Feb;6(2):475–480. doi: 10.1523/JNEUROSCI.06-02-00475.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marty A., Tan Y. P., Trautmann A. Three types of calcium-dependent channel in rat lacrimal glands. J Physiol. 1984 Dec;357:293–325. doi: 10.1113/jphysiol.1984.sp015501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moolenaar W. H., Defize L. H., De Laat S. W. Ionic signalling by growth factor receptors. J Exp Biol. 1986 Sep;124:359–373. doi: 10.1242/jeb.124.1.359. [DOI] [PubMed] [Google Scholar]
  16. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  17. Petersen O. H., Maruyama Y. Calcium-activated potassium channels and their role in secretion. Nature. 1984 Feb 23;307(5953):693–696. doi: 10.1038/307693a0. [DOI] [PubMed] [Google Scholar]
  18. Trautmann A., Marty A. Activation of Ca-dependent K channels by carbamoylcholine in rat lacrimal glands. Proc Natl Acad Sci U S A. 1984 Jan;81(2):611–615. doi: 10.1073/pnas.81.2.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vicentini L. M., Di Virgilio F., Ambrosini A., Pozzan T., Meldolesi J. Tumor promoter phorbol 12-myristate, 13-acetate inhibits phosphoinositide hydrolysis and cytosolic Ca2+ rise induced by the activation of muscarinic receptors in PC12 cells. Biochem Biophys Res Commun. 1985 Feb 28;127(1):310–317. doi: 10.1016/s0006-291x(85)80160-1. [DOI] [PubMed] [Google Scholar]

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