Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 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.

Full text

PDF

Images in this article

2944Image
on p.2944
2945Image
on p.2945

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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES