[Involvement of protein kinase C in the acid secretion of gastric parietal cells].
In isolated parietal cells from gastric fundic mucosa of the rabbit, activation of protein kinase C by the stable diacylglycerol analogue, OAG, and by the phorbol ester, TPA, inhibited in a dose-dependant manner both histamine-stimulated AP accumulation (EC50: 25 microM and 1.6 nM, respectively) and carbachol-stimulated AP accumulation (EC50: 15 microM and 0.6 nM, respectively). Stimulation by forskolin, but not that induced by db-cAMP, was also inhibited. A pretreatment of the cells with cholera toxin caused a reduction of the inhibitory effect of OAG on histamine stimulation, suggesting an action of the PKC on the Gs subunit of the adenylate cyclase. The IP3 generation induced by stimulation of the muscarinic receptor with carbachol was inhibited when the cells were pretreated with TPA. In the same way, the cholinergic-dependent rise of intracellular Ca2+ in parietal cells was dose-dependently inhibited by TPA or OAG and this inhibition was correlated with the inhibition of AP accumulation evaluated in the same conditions. In conclusion, this study demonstrates an involvement of the PKC in the control of the two pathways of the stimulation of acid secretion by a mechanism different from that involved in the negative regulation by prostaglandins.
Choquet
A
A
Laboratoire de biochimie des membranes du CNRS UPR-8402 INSERM U-249, Faculté de Pharmacie, Montpellier.
Magous
R
R
Bali
J P
JP
D000818:Animals; D004075:Diglycerides / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D004075:Diglycerides; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate
Implication de la protéine kinase C dans la sécrétion acide des cellules pariétales gastriques.