Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1988 Dec 1;256(2):677–680. doi: 10.1042/bj2560677

Protein kinase C-dependent and -independent mechanisms regulating the parotid substance P receptor as revealed by differential effects of protein kinase C inhibitors.

H Sugiya 1, J W Putney Jr 1
PMCID: PMC1135464  PMID: 2464997

Abstract

Substance P-induced inositol trisphosphate (InsP3) formation was inhibited by 1 microM-4 beta-phorbol 12,13-dibutyrate (PDBu) in rat parotid acinar cells. The inhibitory effect of PDBu was reversed by the protein kinase C inhibitors H-7 or K252a. Substance P also elicits a persistent desensitization of subsequent substance P-stimulated InsP3 formation. However, this desensitization was not inhibited by H-7. In addition, H-7 had no effect on the time course of substance P-induced InsP3 formation. These results suggest that, although activation of protein kinase C by phorbol esters can inhibit the substance P receptor-linked phospholipase C pathway, this mechanism apparently plays little, if any, role in regulating this system after activation by substance P.

Full text

PDF
677

Selected References

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

  1. Aub D. L., Putney J. W., Jr Metabolism of inositol phosphates in parotid cells: implications for the pathway of the phosphoinositide effect and for the possible messenger role of inositol trisphosphate. Life Sci. 1984 Apr 2;34(14):1347–1355. doi: 10.1016/0024-3205(84)90006-7. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Cooper R. H., Coll K. E., Williamson J. R. Differential effects of phorbol ester on phenylephrine and vasopressin-induced Ca2+ mobilization in isolated hepatocytes. J Biol Chem. 1985 Mar 25;260(6):3281–3288. [PubMed] [Google Scholar]
  5. García-Sáinz J. A., Hernández-Sotomayor S. M. Inhibitors of protein kinase C block the alpha 1-adrenergic refractoriness induced by phorbol 12-myristate 13-acetate, vasopressin and angiotensin II. Eur J Biochem. 1987 Mar 2;163(2):417–421. doi: 10.1111/j.1432-1033.1987.tb10814.x. [DOI] [PubMed] [Google Scholar]
  6. Hanley M. R., Lee C. M., Michell R. H., Jones L. M. Similar effects of substance P and related peptides on salivation and on phosphatidylinositol turnover in rat salivary glands. Mol Pharmacol. 1980 Jul;18(1):78–83. [PubMed] [Google Scholar]
  7. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  8. Johnson R. M., Connelly P. A., Sisk R. B., Pobiner B. F., Hewlett E. L., Garrison J. C. Pertussis toxin or phorbol 12-myristate 13-acetate can distinguish between epidermal growth factor- and angiotensin-stimulated signals in hepatocytes. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2032–2036. doi: 10.1073/pnas.83.7.2032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Kikuchi A., Ikeda K., Kozawa O., Takai Y. Modes of inhibitory action of protein kinase C in the chemotactic peptide-induced formation of inositol phosphates in differentiated human leukemic (HL-60) cells. J Biol Chem. 1987 May 15;262(14):6766–6770. [PubMed] [Google Scholar]
  11. 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]
  12. Liles W. C., Hunter D. D., Meier K. E., Nathanson N. M. Activation of protein kinase C induces rapid internalization and subsequent degradation of muscarinic acetylcholine receptors in neuroblastoma cells. J Biol Chem. 1986 Apr 25;261(12):5307–5313. [PubMed] [Google Scholar]
  13. Merritt J. E., Rink T. J. The effects of substance P and carbachol on inositol tris- and tetrakisphosphate formation and cytosolic free calcium in rat parotid acinar cells. A correlation between inositol phosphate levels and calcium entry. J Biol Chem. 1987 Nov 5;262(31):14912–14916. [PubMed] [Google Scholar]
  14. Muldoon L. L., Jamieson G. A., Jr, Villereal M. L. Calcium mobilization in permeabilized fibroblasts: effects of inositol trisphosphate, orthovanadate, mitogens, phorbol ester, and guanosine triphosphate. J Cell Physiol. 1987 Jan;130(1):29–36. doi: 10.1002/jcp.1041300106. [DOI] [PubMed] [Google Scholar]
  15. Orellana S., Solski P. A., Brown J. H. Guanosine 5'-O-(thiotriphosphate)-dependent inositol trisphosphate formation in membranes is inhibited by phorbol ester and protein kinase C. J Biol Chem. 1987 Feb 5;262(4):1638–1643. [PubMed] [Google Scholar]
  16. Osugi T., Imaizumi T., Mizushima A., Uchida S., Yoshida H. Phorbol ester inhibits bradykinin-stimulated inositol trisphosphate formation and calcium mobilization in neuroblastoma x glioma hybrid NG108-15 cells. J Pharmacol Exp Ther. 1987 Feb;240(2):617–622. [PubMed] [Google Scholar]
  17. Putney J. W., Jr, McKinney J. S., Aub D. L., Leslie B. A. Phorbol ester-induced protein secretion in rat parotid gland. Relationship to the role of inositol lipid breakdown and protein kinase C activation in stimulus-secretion coupling. Mol Pharmacol. 1984 Sep;26(2):261–266. [PubMed] [Google Scholar]
  18. Putney J. W., Jr Muscarinic, alpha-adrenergic and peptide receptors regulate the same calcium influx sites in the parotid gland. J Physiol. 1977 Jun;268(1):139–149. doi: 10.1113/jphysiol.1977.sp011851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sha'afi R. I., Molski T. F., Huang C. K., Naccache P. H. The inhibition of neutrophil responsiveness caused by phorbol esters is blocked by the protein kinase C inhibitor H7. Biochem Biophys Res Commun. 1986 May 29;137(1):50–60. doi: 10.1016/0006-291x(86)91174-5. [DOI] [PubMed] [Google Scholar]
  20. Sibley D. R., Lefkowitz R. J. Molecular mechanisms of receptor desensitization using the beta-adrenergic receptor-coupled adenylate cyclase system as a model. Nature. 1985 Sep 12;317(6033):124–129. doi: 10.1038/317124a0. [DOI] [PubMed] [Google Scholar]
  21. Smith C. D., Uhing R. J., Snyderman R. Nucleotide regulatory protein-mediated activation of phospholipase C in human polymorphonuclear leukocytes is disrupted by phorbol esters. J Biol Chem. 1987 May 5;262(13):6121–6127. [PubMed] [Google Scholar]
  22. Sugiya H., Obie J. F., Putney J. W., Jr Two modes of regulation of the phospholipase C-linked substance-P receptor in rat parotid acinar cells. Biochem J. 1988 Jul 15;253(2):459–466. doi: 10.1042/bj2530459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sugiya H., Tennes K. A., Putney J. W., Jr Homologous desensitization of substance-P-induced inositol polyphosphate formation in rat parotid acinar cells. Biochem J. 1987 Jun 15;244(3):647–653. doi: 10.1042/bj2440647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Toews M. L., Liang M., Perkins J. P. Agonists and phorbol esters desensitize beta-adrenergic receptors by different mechanisms. Mol Pharmacol. 1987 Dec;32(6):737–742. [PubMed] [Google Scholar]
  25. Tohmatsu T., Hattori H., Nagao S., Ohki K., Nozawa Y. Reversal by protein kinase C inhibitor of suppressive actions of phorbol-12-myristate-13-acetate on polyphosphoinositide metabolism and cytosolic Ca2+ mobilization in thrombin-stimulated human platelets. Biochem Biophys Res Commun. 1986 Jan 29;134(2):868–875. doi: 10.1016/s0006-291x(86)80500-9. [DOI] [PubMed] [Google Scholar]
  26. Weiss S. J., McKinney J. S., Putney J. W., Jr Receptor-mediated net breakdown of phosphatidylinositol 4,5-bisphosphate in parotid acinar cells. Biochem J. 1982 Sep 15;206(3):555–560. doi: 10.1042/bj2060555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yamada K., Iwahashi K., Kase H. K252a, a new inhibitor of protein kinase C, concomitantly inhibits 40K protein phosphorylation and serotonin secretion in a phorbol ester-stimulated platelets. Biochem Biophys Res Commun. 1987 Apr 14;144(1):35–40. doi: 10.1016/s0006-291x(87)80471-0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES