Abstract
In bovine adrenal chromaffin cells, prostaglandin E2 (PGE2) stimulates the formation of inositol phosphates and Ca2+ mobilization through its specific receptor [Yokohama, Tanaka, Ito, Negishi, Hayashi & Hayaishi (1988) J. Biol. Chem. 263, 1119-1122]. Here we show that PGE2-induced phosphoinositide metabolism was blocked by pretreatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). Using intact cells, we also examined the inhibitory effect of TPA on the individual steps of the activation process of phosphoinositide metabolism. The inhibition was observed within 1 min and complete by 10 min after addition of 1 microM-TPA, and half-maximal inhibition by TPA occurred at 20 nM. TPA prevented Ca2+ mobilization induced by PGE2, but not by the Ca2+ ionophore ionomycin. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate did not inhibit the formation of inositol phosphates and Ca2+ mobilization by PGE2. TPA treatment affected neither the high-affinity binding of [3H]PGE2 to intact cells and membrane fractions nor the ability of guanosine 5'-[gamma-thio]triphosphate to decrease the binding in membrane fractions. TPA also abolished phosphoinositide metabolism induced by muscarinic-receptor activation. NaF plus AlCl3 and ionomycin caused the accumulation of inositol phosphates, probably by directly activating a GTP-binding protein(s) and phospholipase C respectively; neither accumulation was inhibited by TPA treatment. These results suggest that protein kinase C serves as a feedback regulator for PGE2-induced phosphoinositide metabolism. The site of action of TPA appears to be distal to the coupling of the receptor to GTP-binding protein, but on a component(s) specific to the agonist-induced phosphoinositide metabolism.
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- Anthes J. C., Billah M. M., Cali A., Egan R. W., Siegel M. I. Chemotactic peptide, calcium and guanine nucleotide regulation of phospholipase C activity in membranes from DMSO-differentiated HL60 cells. Biochem Biophys Res Commun. 1987 Jun 15;145(2):825–833. doi: 10.1016/0006-291x(87)91039-4. [DOI] [PubMed] [Google Scholar]
- 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]
- Blackmore P. F., Bocckino S. B., Waynick L. E., Exton J. H. Role of a guanine nucleotide-binding regulatory protein in the hydrolysis of hepatocyte phosphatidylinositol 4,5-bisphosphate by calcium-mobilizing hormones and the control of cell calcium. Studies utilizing aluminum fluoride. J Biol Chem. 1985 Nov 25;260(27):14477–14483. [PubMed] [Google Scholar]
- 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]
- 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]
- Eberhard D. A., Holz R. W. Cholinergic stimulation of inositol phosphate formation in bovine adrenal chromaffin cells: distinct nicotinic and muscarinic mechanisms. J Neurochem. 1987 Nov;49(5):1634–1643. doi: 10.1111/j.1471-4159.1987.tb01037.x. [DOI] [PubMed] [Google Scholar]
- Forsberg E. J., Rojas E., Pollard H. B. Muscarinic receptor enhancement of nicotine-induced catecholamine secretion may be mediated by phosphoinositide metabolism in bovine adrenal chromaffin cells. J Biol Chem. 1986 Apr 15;261(11):4915–4920. [PubMed] [Google Scholar]
- Gomperts B. D. Involvement of guanine nucleotide-binding protein in the gating of Ca2+ by receptors. Nature. 1983 Nov 3;306(5938):64–66. doi: 10.1038/306064a0. [DOI] [PubMed] [Google Scholar]
- 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]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- 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]
- Lynch C. J., Charest R., Bocckino S. B., Exton J. H., Blackmore P. F. Inhibition of hepatic alpha 1-adrenergic effects and binding by phorbol myristate acetate. J Biol Chem. 1985 Mar 10;260(5):2844–2851. [PubMed] [Google Scholar]
- Majerus P. W., Connolly T. M., Deckmyn H., Ross T. S., Bross T. E., Ishii H., Bansal V. S., Wilson D. B. The metabolism of phosphoinositide-derived messenger molecules. Science. 1986 Dec 19;234(4783):1519–1526. doi: 10.1126/science.3024320. [DOI] [PubMed] [Google Scholar]
- Misbahuddin M., Isosaki M., Houchi H., Oka M. Muscarinic receptor-mediated increase in cytoplasmic free Ca2+ in isolated bovine adrenal medullary cells. Effects of TMB-8 and phorbol ester TPA. FEBS Lett. 1985 Oct 7;190(1):25–28. doi: 10.1016/0014-5793(85)80419-1. [DOI] [PubMed] [Google Scholar]
- Negishi M., Ito S., Tanaka T., Yokohama H., Hayashi H., Katada T., Ui M., Hayaishi O. Covalent cross-linking of prostaglandin E receptor from bovine adrenal medulla with a pertussis toxin-insensitive guanine nucleotide-binding protein. J Biol Chem. 1987 Sep 5;262(25):12077–12084. [PubMed] [Google Scholar]
- Negishi M., Ito S., Yokohama H., Hayashi H., Katada T., Ui M., Hayaishi O. Functional reconstitution of prostaglandin E receptor from bovine adrenal medulla with guanine nucleotide binding proteins. J Biol Chem. 1988 May 15;263(14):6893–6900. [PubMed] [Google Scholar]
- Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
- Orellana S. A., Solski P. A., Brown J. H. Phorbol ester inhibits phosphoinositide hydrolysis and calcium mobilization in cultured astrocytoma cells. J Biol Chem. 1985 May 10;260(9):5236–5239. [PubMed] [Google Scholar]
- Paris S., Pouysségur J. Further evidence for a phospholipase C-coupled G protein in hamster fibroblasts. Induction of inositol phosphate formation by fluoroaluminate and vanadate and inhibition by pertussis toxin. J Biol Chem. 1987 Feb 15;262(5):1970–1976. [PubMed] [Google Scholar]
- Pfeilschifter J., Bauer C. Different effects of phorbol ester on angiotensin II- and stable GTP analogue-induced activation of polyphosphoinositide phosphodiesterase in membranes isolated from rat renal mesangial cells. Biochem J. 1987 Nov 15;248(1):209–215. doi: 10.1042/bj2480209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfeilschifter J. Tumour promotor 12-O-tetradecanoylphorbol 13-acetate inhibits angiotensin II-induced inositol phosphate production and cytosolic Ca2+ rise in rat renal mesangial cells. FEBS Lett. 1986 Jul 28;203(2):262–266. doi: 10.1016/0014-5793(86)80755-4. [DOI] [PubMed] [Google Scholar]
- Samuelsson B., Goldyne M., Granström E., Hamberg M., Hammarström S., Malmsten C. Prostaglandins and thromboxanes. Annu Rev Biochem. 1978;47:997–1029. doi: 10.1146/annurev.bi.47.070178.005025. [DOI] [PubMed] [Google Scholar]
- Sasakawa N., Nakaki T., Yamamoto S., Kato R. Inositol trisphosphate accumulation by high K+ stimulation in cultured adrenal chromaffin cells. FEBS Lett. 1987 Nov 2;223(2):413–416. doi: 10.1016/0014-5793(87)80330-7. [DOI] [PubMed] [Google Scholar]
- Seyfred M. A., Farrell L. E., Wells W. W. Characterization of D-myo-inositol 1,4,5-trisphosphate phosphatase in rat liver plasma membranes. J Biol Chem. 1984 Nov 10;259(21):13204–13208. [PubMed] [Google Scholar]
- Sortino M., Canonico P. L., Summers S. T., Cronin M. J. Protein kinase C inhibits TRH-stimulated phosphoinositide hydrolysis in GH3 cells. Eur J Pharmacol. 1987 Mar 3;135(1):77–83. doi: 10.1016/0014-2999(87)90759-x. [DOI] [PubMed] [Google Scholar]
- Strnad C. F., Parente J. E., Wong K. Use of fluoride ion as a probe for the guanine nucleotide-binding protein involved in the phosphoinositide-dependent neutrophil transduction pathway. FEBS Lett. 1986 Sep 29;206(1):20–24. doi: 10.1016/0014-5793(86)81332-1. [DOI] [PubMed] [Google Scholar]
- Tanaka T., Yokohama H., Negishi M., Hayashi H., Ito S., Hayaishi O. Pertussis toxin facilitates secretagogue-induced catecholamine release from cultured bovine adrenal chromaffin cells. Biochem Biophys Res Commun. 1987 Apr 29;144(2):907–914. doi: 10.1016/s0006-291x(87)80050-5. [DOI] [PubMed] [Google Scholar]
- Uhing R. J., Prpic V., Jiang H., Exton J. H. Hormone-stimulated polyphosphoinositide breakdown in rat liver plasma membranes. Roles of guanine nucleotides and calcium. J Biol Chem. 1986 Feb 15;261(5):2140–2146. [PubMed] [Google Scholar]
- 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]
- Yokohama H., Tanaka T., Ito S., Negishi M., Hayashi H., Hayaishi O. Prostaglandin E receptor enhancement of catecholamine release may be mediated by phosphoinositide metabolism in bovine adrenal chromaffin cells. J Biol Chem. 1988 Jan 25;263(3):1119–1122. [PubMed] [Google Scholar]
- Zavoico G. B., Halenda S. P., Sha'afi R. I., Feinstein M. B. Phorbol myristate acetate inhibits thrombin-stimulated Ca2+ mobilization and phosphatidylinositol 4,5-bisphosphate hydrolysis in human platelets. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3859–3862. doi: 10.1073/pnas.82.11.3859. [DOI] [PMC free article] [PubMed] [Google Scholar]