Interaction of signal transduction pathways in mediating acid secretion by rat parietal cells.
To examine the role of protein kinase C (PKC) on the acid secretory activity of isolated rat parietal cells, histamine-and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-stimulated [14C]aminopyrine accumulation was determined in the presence of agents that redistribute PKC activity to plasma membranes. Phorbol 12-myristate 13-acetate (PMA), 1-oleoyl-2-acetylglycerol (OAG), and phospholipase C inhibited, in a dose-dependent fashion, histamine- and DBcAMP-stimulated [14C]aminopyrine accumulation. Because PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) reversed the effect, the results suggest that inhibition of histamine- or DBcAMP-stimulated [14C]aminopyrine accumulation induced by PMA, OAG, or phospholipase C was caused by increased activity of PKC in plasma membrane. To determine where in the cascade of events PKC inhibits acid secretion, histamine-, cholera toxin-, and forskolin-stimulated [14C]aminopyrine accumulation was measured with or without PMA. Because the percent of inhibition by PMA of [14C]aminopyrine accumulation was similar with the three secretagogues, the results suggest that PKC inhibits acid secretion at a point beyond adenosine 3',5'-cyclic monophosphate (cAMP) production. This was supported by the fact that PMA had no effect on histamine-stimulated production of cAMP and by the finding that activation of PKC had the same effect on histamine- or DBcAMP-stimulated [14C]aminopyrine accumulation. Histamine and DBcAMP inhibited PKC activity, suggesting a reciprocal interaction between PKC and histamine-triggered signal transduction pathway.
Ostrowski
J
J
Department of Medicine, University of Washington, Seattle 98195.
Bomsztyk
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D004075:Diglycerides / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000494:pharmacology
D004075:Diglycerides; D007546:Isoquinolines; D010879:Piperazines; D000632:Aminopyrine; D003994:Bucladesine; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine