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. 1989 Apr;86(8):2943–2947. doi: 10.1073/pnas.86.8.2943

Protein kinase C is not necessary for peptide-induced suppression of M current or for desensitization of the peptide receptors.

M M Bosma 1, B Hille 1
PMCID: PMC287036  PMID: 2468164

Abstract

Frog sympathetic ganglion cells were studied under whole-cell voltage clamp to determine whether protein kinase C (PKC) mediates peptide-induced suppression of M current (IM) or desensitization of peptide receptors. Low concentrations (10 mM) of chicken II luteinizing hormone-releasing hormone (LHRH) or substance P (SP) suppressed IM; in addition, higher concentrations (1 microM) desensitized receptors. Desensitization is homologous (specific to the peptide) and lasts at least 25 min. Two stimulators of PKC, phorbol 12-myristate 13-acetate and dioctanoylglycerol, partially depressed IM and occluded the response to SP but not to LHRH. The two actions of PKC stimulators were blocked by PKC inhibitors (staurosporine, a pseudosubstrate peptide, and H-7), but SP- and LHRH-mediated suppression of IM and receptor desensitization were not affected. Thus, we conclude that PKC is not necessary for normal IM suppression or receptor desensitization.

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Selected References

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

  1. Adams P. R., Brown D. A., Constanti A. M-currents and other potassium currents in bullfrog sympathetic neurones. J Physiol. 1982 Sep;330:537–572. doi: 10.1113/jphysiol.1982.sp014357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams P. R., Brown D. A., Jones S. W. Substance P inhibits the M-current in bullfrog sympathetic neurones. Br J Pharmacol. 1983 Jun;79(2):330–333. doi: 10.1111/j.1476-5381.1983.tb11004.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adams P. R., Brown D. A. Luteinizing hormone-releasing factor and muscarinic agonists act on the same voltage-sensitive K+-current in bullfrog sympathetic neurones. Br J Pharmacol. 1980 Mar;68(3):353–355. doi: 10.1111/j.1476-5381.1980.tb14547.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Aiyar N., Nambi P., Whitman M., Stassen F. L., Crooke S. T. Phorbol ester-mediated inhibition of vasopressin and beta-adrenergic responses in a vascular smooth muscle cell line. Mol Pharmacol. 1987 Feb;31(2):180–184. [PubMed] [Google Scholar]
  5. Benovic J. L., Strasser R. H., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc Natl Acad Sci U S A. 1986 May;83(9):2797–2801. doi: 10.1073/pnas.83.9.2797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bouvier M., Hausdorff W. P., De Blasi A., O'Dowd B. F., Kobilka B. K., Caron M. G., Lefkowitz R. J. Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization. Nature. 1988 May 26;333(6171):370–373. doi: 10.1038/333370a0. [DOI] [PubMed] [Google Scholar]
  7. Bouvier M., Leeb-Lundberg L. M., Benovic J. L., Caron M. G., Lefkowitz R. J. Regulation of adrenergic receptor function by phosphorylation. II. Effects of agonist occupancy on phosphorylation of alpha 1- and beta 2-adrenergic receptors by protein kinase C and the cyclic AMP-dependent protein kinase. J Biol Chem. 1987 Mar 5;262(7):3106–3113. [PubMed] [Google Scholar]
  8. Brown D. A., Adams P. R. Effects of phorbol dibutyrate on M currents and M current inhibition in bullfrog sympathetic neurons. Cell Mol Neurobiol. 1987 Sep;7(3):255–269. doi: 10.1007/BF00711303. [DOI] [PubMed] [Google Scholar]
  9. Brown D. A., Adams P. R. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature. 1980 Feb 14;283(5748):673–676. doi: 10.1038/283673a0. [DOI] [PubMed] [Google Scholar]
  10. Brown D. A., Higashida H. Inositol 1,4,5-trisphosphate and diacylglycerol mimic bradykinin effects on mouse neuroblastoma x rat glioma hybrid cells. J Physiol. 1988 Mar;397:185–207. doi: 10.1113/jphysiol.1988.sp016995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Brown D. M-currents: an update. Trends Neurosci. 1988 Jul;11(7):294–299. doi: 10.1016/0166-2236(88)90089-6. [DOI] [PubMed] [Google Scholar]
  12. Cambier J., Chen Z. Z., Pasternak J., Ransom J., Sandoval V., Pickles H. Ligand-induced desensitization of B-cell membrane immunoglobulin-mediated Ca2+ mobilization and protein kinase C translocation. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6493–6497. doi: 10.1073/pnas.85.17.6493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dutar P., Nicoll R. A. Stimulation of phosphatidylinositol (PI) turnover may mediate the muscarinic suppression of the M-current in hippocampal pyramidal cells. Neurosci Lett. 1988 Feb 15;85(1):89–94. doi: 10.1016/0304-3940(88)90434-x. [DOI] [PubMed] [Google Scholar]
  14. Higashida H., Brown D. A. Two polyphosphatidylinositide metabolites control two K+ currents in a neuronal cell. 1986 Sep 25-Oct 1Nature. 323(6086):333–335. doi: 10.1038/323333a0. [DOI] [PubMed] [Google Scholar]
  15. House C., Kemp B. E. Protein kinase C contains a pseudosubstrate prototope in its regulatory domain. Science. 1987 Dec 18;238(4834):1726–1728. doi: 10.1126/science.3686012. [DOI] [PubMed] [Google Scholar]
  16. Jan L. Y., Jan Y. N. Peptidergic transmission in sympathetic ganglia of the frog. J Physiol. 1982 Jun;327:219–246. doi: 10.1113/jphysiol.1982.sp014228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jan Y. N., Jan L. Y., Kuffler S. W. A peptide as a possible transmitter in sympathetic ganglia of the frog. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1501–1505. doi: 10.1073/pnas.76.3.1501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jan Y. N., Jan L. Y., Kuffler S. W. Further evidence for peptidergic transmission in sympathetic ganglia. Proc Natl Acad Sci U S A. 1980 Aug;77(8):5008–5012. doi: 10.1073/pnas.77.8.5008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jones S. W. Chicken II luteinizing hormone-releasing hormone inhibits the M-current of bullfrog sympathetic neurons. Neurosci Lett. 1987 Sep 23;80(2):180–184. doi: 10.1016/0304-3940(87)90650-1. [DOI] [PubMed] [Google Scholar]
  20. Jones S. W. Muscarinic and peptidergic excitation of bull-frog sympathetic neurones. J Physiol. 1985 Sep;366:63–87. doi: 10.1113/jphysiol.1985.sp015785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Kawamoto S., Hidaka H. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7) is a selective inhibitor of protein kinase C in rabbit platelets. Biochem Biophys Res Commun. 1984 Nov 30;125(1):258–264. doi: 10.1016/s0006-291x(84)80362-9. [DOI] [PubMed] [Google Scholar]
  23. Kühn H., Dreyer W. J. Light dependent phosphorylation of rhodopsin by ATP. FEBS Lett. 1972 Jan 15;20(1):1–6. doi: 10.1016/0014-5793(72)80002-4. [DOI] [PubMed] [Google Scholar]
  24. Leeb-Lundberg L. M., Cotecchia S., DeBlasi A., Caron M. G., Lefkowitz R. J. Regulation of adrenergic receptor function by phosphorylation. I. Agonist-promoted desensitization and phosphorylation of alpha 1-adrenergic receptors coupled to inositol phospholipid metabolism in DDT1 MF-2 smooth muscle cells. J Biol Chem. 1987 Mar 5;262(7):3098–3105. [PubMed] [Google Scholar]
  25. Moskowitz M. A., Kuo C., Leeman S. E., Jessen M. E., Derian C. K. Desensitization to substance P-induced vasodilation in vitro is not shared by endogenous tachykinin neurokinin A. J Neurosci. 1987 Aug;7(8):2344–2351. [PMC free article] [PubMed] [Google Scholar]
  26. Pfaffinger P. J., Leibowitz M. D., Subers E. M., Nathanson N. M., Almers W., Hille B. Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. Neuron. 1988 Aug;1(6):477–484. doi: 10.1016/0896-6273(88)90178-x. [DOI] [PubMed] [Google Scholar]
  27. Pfaffinger P. Muscarine and t-LHRH suppress M-current by activating an IAP-insensitive G-protein. J Neurosci. 1988 Sep;8(9):3343–3353. doi: 10.1523/JNEUROSCI.08-09-03343.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Satoh S., Itoh T., Kuriyama H. Actions of angiotensin II and noradrenaline on smooth muscle cells of the canine mesenteric artery. Pflugers Arch. 1987 Sep;410(1-2):132–138. doi: 10.1007/BF00581905. [DOI] [PubMed] [Google Scholar]
  30. Tamaoki T., Nomoto H., Takahashi I., Kato Y., Morimoto M., Tomita F. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun. 1986 Mar 13;135(2):397–402. doi: 10.1016/0006-291x(86)90008-2. [DOI] [PubMed] [Google Scholar]
  31. Vegesna R. V., Wu H. L., Mong S., Crooke S. T. Staurosporine inhibits protein kinase C and prevents phorbol ester-mediated leukotriene D4 receptor desensitization in RBL-1 cells. Mol Pharmacol. 1988 May;33(5):537–542. [PubMed] [Google Scholar]

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