Protein kinase C modulates effects of prostanoids on cyclic adenosine monophosphate in guinea pig chief cells.
In the course of examining the role of protein kinase C in signal transduction in dispersed chief cells from guinea pig stomach, we observed that phorbol esters inhibit prostaglandin (PG)-stimulated increases in cyclic adenosine monophosphate (cAMP). Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, decreased maximal levels of PGE2-stimulated cAMP by 40%. This dose-dependent effect was observed within 30 sec and was maximal by 1 min of incubation at 37 degrees C. Phorbols that do not activate protein kinase C did not have this effect. Adding H7, a protein kinase C inhibitor, abolished the inhibitory effects of PMA, indicating that these effects are not caused by activation of cyclic nucleotide phosphodiesterases. PMA did not alter the increase in cellular cAMP caused by cholera toxin, forskolin, secretin, or vasoactive intestinal peptide. Hence the site of these prostanoid-specific actions of protein kinase C does not appear to be stimulatory or inhibitory guanine nucleotide binding proteins or the catalytic component of the adenylyl cyclase system. In dispersed chief cells, activation of protein kinase C may inhibit prostanoid-induced stimulation of the adenylyl cyclase system by a direct effect on prostaglandin receptors.
Raufman
J P
JP
Department of Medicine, State University of New York Brooklyn 11203.
Cosowsky
L
L
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism*; D006168:Guinea Pigs; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010435:Pepsinogens / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011863:Radioimmunoassay; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D007546:Isoquinolines; D010435:Pepsinogens; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate