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
. 1985 Jan;82(2):604–607. doi: 10.1073/pnas.82.2.604

Phorbol ester effects on neurotransmission: interaction with neurotransmitters and calcium in smooth muscle.

J M Baraban, R J Gould, S J Peroutka, S H Snyder
PMCID: PMC397089  PMID: 2857490

Abstract

Stimulation of the phosphatidylinositol cycle by neurotransmitters generates diacylglycerol, an activator of protein kinase C, which may regulate some forms of neurotransmission. Phorbol esters, potent inflammatory and tumor-promoting compounds, also activate protein kinase C. We demonstrate potent and selective effects of phorbol esters on smooth muscle, indicating a role for protein kinase C in neurotransmission. In rat vas deferens and dog basilar artery, phorbol esters synergize with calcium to mimic the contractile effects of neurotransmitters that act through the phosphatidylinositol cycle. In guinea pig ileum and rat uterus, phorbol esters block contractions produced by these neurotransmitters.

Full text

PDF
607

Selected References

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

  1. Aloyo V. J., Zwiers H., Gispen W. H. Phosphorylation of B-50 protein by calcium-activated, phospholipid-dependent protein kinase and B-50 protein kinase. J Neurochem. 1983 Sep;41(3):649–653. doi: 10.1111/j.1471-4159.1983.tb04790.x. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blumberg P. M., Jaken S., König B., Sharkey N. A., Leach K. L., Jeng A. Y., Yeh E. Mechanism of action of the phorbol ester tumor promoters: specific receptors for lipophilic ligands. Biochem Pharmacol. 1984 Mar 15;33(6):933–940. doi: 10.1016/0006-2952(84)90448-9. [DOI] [PubMed] [Google Scholar]
  4. Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
  5. Burgess G. M., Godfrey P. P., McKinney J. S., Berridge M. J., Irvine R. F., Putney J. W., Jr The second messenger linking receptor activation to internal Ca release in liver. Nature. 1984 May 3;309(5963):63–66. doi: 10.1038/309063a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Costa M., Furness J. B. The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon. Br J Pharmacol. 1979 Feb;65(2):237–248. doi: 10.1111/j.1476-5381.1979.tb07824.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Driedger P. E., Blumberg P. M. Specific binding of phorbol ester tumor promoters. Proc Natl Acad Sci U S A. 1980 Jan;77(1):567–571. doi: 10.1073/pnas.77.1.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dunn J. A., Blumberg P. M. Specific binding of [20-3H]12-deoxyphorbol 13-isobutyrate to phorbol ester receptor subclasses in mouse skin particulate preparations. Cancer Res. 1983 Oct;43(10):4632–4637. [PubMed] [Google Scholar]
  10. Hong S. L., Deykin D. Activation of phospholipases A2 and C in pig aortic endothelial cells synthesizing prostacyclin. J Biol Chem. 1982 Jun 25;257(12):7151–7154. [PubMed] [Google Scholar]
  11. Inoue M., Kishimoto A., Takai Y., Nishizuka Y. Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. II. Proenzyme and its activation by calcium-dependent protease from rat brain. J Biol Chem. 1977 Nov 10;252(21):7610–7616. [PubMed] [Google Scholar]
  12. Jolles J., Zwiers H., Dekker A., Wirtz K. W., Gispen W. H. Corticotropin-(1--24)-tetracosapeptide affects protein phosphorylation and polyphosphoinositide metabolism in rat brain. Biochem J. 1981 Jan 15;194(1):283–291. doi: 10.1042/bj1940283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jolles J., Zwiers H., van Dongen C. J., Schotman P., Wirtz K. W., Gispen W. H. Modulation of brain polyphosphoinositide metabolism by ACTH-sensitive protein phosphorylation. Nature. 1980 Aug 7;286(5773):623–625. doi: 10.1038/286623a0. [DOI] [PubMed] [Google Scholar]
  14. Kikkawa U., Takai Y., Tanaka Y., Miyake R., Nishizuka Y. Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters. J Biol Chem. 1983 Oct 10;258(19):11442–11445. [PubMed] [Google Scholar]
  15. Kishimoto A., Takai Y., Mori T., Kikkawa U., Nishizuka Y. Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover. J Biol Chem. 1980 Mar 25;255(6):2273–2276. [PubMed] [Google Scholar]
  16. Labarca R., Janowsky A., Patel J., Paul S. M. Phorbol esters inhibit agonist-induced [3H] inositol-1-phosphate accumulation in rat hippocampal slices. Biochem Biophys Res Commun. 1984 Sep 17;123(2):703–709. doi: 10.1016/0006-291x(84)90286-9. [DOI] [PubMed] [Google Scholar]
  17. Leach K. L., James M. L., Blumberg P. M. Characterization of a specific phorbol ester aporeceptor in mouse brain cytosol. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4208–4212. doi: 10.1073/pnas.80.14.4208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Michell R. H. Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta. 1975 Mar 25;415(1):81–47. doi: 10.1016/0304-4157(75)90017-9. [DOI] [PubMed] [Google Scholar]
  19. Mori T., Takai Y., Yu B., Takahashi J., Nishizuka Y., Fujikura T. Specificity of the fatty acyl moieties of diacylglycerol for the activation of calcium-activated, phospholipid-dependent protein kinase. J Biochem. 1982 Feb;91(2):427–431. doi: 10.1093/oxfordjournals.jbchem.a133714. [DOI] [PubMed] [Google Scholar]
  20. Niedel J. E., Kuhn L. J., Vandenbark G. R. Phorbol diester receptor copurifies with protein kinase C. Proc Natl Acad Sci U S A. 1983 Jan;80(1):36–40. doi: 10.1073/pnas.80.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Peroutka S. J., Noguchi M., Tolner D. J., Allen G. S. Serotonin-induced contraction of canine basilar artery: mediation by 5-HT1 receptors. Brain Res. 1983 Jan 24;259(2):327–330. doi: 10.1016/0006-8993(83)91268-4. [DOI] [PubMed] [Google Scholar]
  22. Shoyab M., Todaro G. J. Specific high affinity cell membrane receptors for biologically active phorbol and ingenol esters. Nature. 1980 Dec 4;288(5790):451–455. doi: 10.1038/288451a0. [DOI] [PubMed] [Google Scholar]
  23. Streb H., Irvine R. F., Berridge M. J., Schulz I. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature. 1983 Nov 3;306(5938):67–69. doi: 10.1038/306067a0. [DOI] [PubMed] [Google Scholar]
  24. Takai Y., Kishimoto A., Inoue M., Nishizuka Y. Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. I. Purification and characterization of an active enzyme from bovine cerebellum. J Biol Chem. 1977 Nov 10;252(21):7603–7609. [PubMed] [Google Scholar]
  25. Takai Y., Kishimoto A., Kikkawa U., Mori T., Nishizuka Y. Unsaturated diacylglycerol as a possible messenger for the activation of calcium-activated, phospholipid-dependent protein kinase system. Biochem Biophys Res Commun. 1979 Dec 28;91(4):1218–1224. doi: 10.1016/0006-291x(79)91197-5. [DOI] [PubMed] [Google Scholar]
  26. Triggle D. J. Adrenergic receptors. Annu Rev Pharmacol. 1972;12:185–196. doi: 10.1146/annurev.pa.12.040172.001153. [DOI] [PubMed] [Google Scholar]
  27. Yamanishi J., Takai Y., Kaibuchi K., Sano K., Castagna M., Nishizuka Y. Synergistic functions of phorbol ester and calcium in serotonin release from human platelets. Biochem Biophys Res Commun. 1983 Apr 29;112(2):778–786. doi: 10.1016/0006-291x(83)91529-2. [DOI] [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