Sites of action of protein kinase C on secretory activity in rat parietal cells.
Sites at which the calcium-sensitive phospholipid-dependent protein kinase, protein kinase C, may influence acid secretion have been investigated in rat isolated parietal cells. In both crude and enriched preparations of parietal cells incubated in a medium containing 100 mM K+, the activators of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA) and 1-oleoyl-2-acetyl-glycerol (OAG), produced a dose-dependent stimulation [half-maximally effective concentration (EC50) values of 1 nM and 70 microM, respectively] of aminopyrine accumulation, an index of the sequestration of acid in the cell. In a medium containing 4.5 mM K+, and with no added secretagogues, TPA and OAG did not affect aminopyrine accumulation. Histamine-stimulated aminopyrine accumulation was inhibited by TPA [half-maximally effective inhibitory concentration (IC50) of 2.9 nM]. TPA reduced the histamine-stimulation of the adenosine 3',5'-cyclic monophosphate (cAMP) content of parietal cells (47% inhibition at 100 nM TPA) but also inhibited aminopyrine accumulation at or distal to cAMP-dependent protein kinase. Activators of protein kinase C can produce multiple effects on secretory activity in the rat parietal cell.
Hatt
J F
JF
Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom.
Hanson
P J
PJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013861:Thiocyanates / Q000494:pharmacology
D002352:Carrier Proteins; D004075:Diglycerides; D017923:Sodium-Hydrogen Exchangers; D013861:Thiocyanates; D000632:Aminopyrine; C024553:sodium thiocyanate; D003994:Bucladesine; D006632:Histamine; C038237:1-oleoyl-2-acetylglycerol; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine