[Modulation of the adenylate cyclase-cAMP pathway by protein kinase C in chick retinal pigment epithelium].
I investigated stimulation of cyclic adenosine 3':5'-monophosphate (cAMP) production by isoproterenol and forskolin in cultured chick embryo retinal pigment epithelium. In addition, in order to study the interaction between signal transduction systems, I studied the effects of phorbol 12-myristate, 13-acetate (PMA), a protein kinase C (PKC) activator, on isoproterenol- or forskolin-stimulated cAMP production. After stimulation with 10(-9)-10(-5) M isoproterenol and forskolin, a marked and concentration-dependent increase in cAMP level was observed. However, addition of 10(-10)-10(-5) M PMA had no effect on the cAMP level. Preincubation of isoproterenol and forskolin with 100 nM PMA suppressed the increase of cAMP. The suppressive effect of PMA was stronger on isoproterenol-stimulated production than on forskolin-stimulated production. 4 alpha-phorbol 12, 13, didecanoate, a weak activator of PKC, had a weak suppressive effect on cAMP-production stimulated by isoproterenol. Both staurosporin and H-7, 1-(5-isoquinolinylsulfonyl)-methylpiperazine, inhibitors of PKC, decreased the suppression of cAMP production by PMA. It is speculated that in chick retinal pigment epithelium PKC stimulators, such as PMA, may inhibit the adenylate cyclase pathway.
Hirota
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Department of Ophthalmology, Hiroshima University School of Medicine, Japan.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate