Inhibition of carbachol stimulated acid secretion by interleukin 1β in rabbit parietal cells requires protein kinase C

Abstract

BACKGROUNDInterleukin 1β (IL-1β) is a potent inhibitor of gastric acid secretion. Regulatory actions at several levels have previously been demonstrated, including direct inhibition of parietal cell acid secretion. Although IL-1β may activate several intracellular signalling pathways, the mechanisms responsible for inhibition of carbachol stimulated acid secretion have not been determined.AIMSTo investigate the roles of protein kinase C (PKC) and the sphingomyelinase signalling pathways in the regulation of acid secretion by IL-1β.METHODSRabbit parietal cells were obtained by collagenase-EDTA digestion and centrifugal elutriation. Acid secretion stimulated by carbachol andA23187 (to mimic elevations in intracellular calcium) was assessed by14C aminopyrine uptake in response to IL-1β, PKC, and sphingomyelinase manipulation.RESULTSIL-1β inhibited carbachol and A23187 stimulated acid secretion in a dose dependent manner. The inhibitory actions were completely reversed by each of three different PKC inhibitors, staurosporine, H-7, and chelerythrine, as well as by PKC depletion with high dose phorbol ester pretreatment. IL-1β did not downregulate parietal cell muscarinic receptor. IL-1β significantly increased membrane PKC activity. Activation of the sphingomyelinase/ceramide pathway had no effect on basal or stimulated acid secretion. The inhibitory action of IL-1β was independent of protein kinase A and protein kinase G activity.CONCLUSIONSIL-1β directly inhibits parietal cell carbachol stimulated acid secretion. This action occurs distal to muscarinic receptor activation and elevations in intracellular calcium and requires PKC.