A G-protein mediates secretagogue-induced gap junctional channel closure in pancreatic acinar cells.

Using the double whole-cell patch-clamp technique, we determined that dialysis of cell pairs by GTP[S] potentiated electrical uncoupling induced by extracellular addition of carbamylcholine (CCh). An inhibitor of diglyceride lipase, RHC 80267, further potentiated CCh/GTP[S]-induced junctional channel closure, probably by accumulation of diacylglycerol. Moreover, the protein kinase C inhibitor polymyxin B completely blocked uncoupling elicited by CCh/GTP[S]. These results provide the first evidence suggesting that gap junction channel closure by cholinergic stimulation is mediated by a G-protein, which acts by increasing phosphatidylinositol biphosphate breakdown and protein kinase C activity.