BACKGROUND Interleukin 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.

AIMS To investigate the roles of protein kinase C (PKC) and the sphingomyelinase signalling pathways in the regulation of acid secretion by IL-1β.

RESULTS IL-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.

CONCLUSIONS IL-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.