LITHOCHOLYLTAURINE INTERACTS WITH CHOLINERGIC RECEPTORS ON DISPERSED CHIEF CELLS FROM GUINEA-PIG STOMACH

Although bile acids damage gastric mucosa, the mechanisms underlying t issue injury induced by these agents are not well understood. To deter mine whether bile acids alter gastric secretory function, we investiga ted the actions of sodium cholate, deoxycholate, lithocholate, and the ir taurine and glycine conjugates on a highly homogeneous population o f gastric chief cells. Lithocholyltaurine (LCT), a particularly injuri ous bile acid, caused a threefold increase in pepsinogen secretion (de tectable with 100 nM and maximal with 10 mu M LCT). When combined with other secretagogues, increasing concentrations of LCT caused progress ive inhibition of carbamylcholine (carbachol)-induced pepsinogen secre tion but did not alter CCK-or 8-bromo-cAMP-induced secretion. Taurine and unconjugated lithocholate did not alter basal or carbachol-induced secretion. These observations suggested that LCT is a partial choline rgic agonist. To test this hypothesis, we examined the actions of the cholinergic antagonist atropine on LCT-induced pepsinogen secretion. A tropine (10 mu M) abolished carbachol-and LCT-induced pepsinogen secre tion. Likewise, carbachol (0.1 mM) and LCT (1 mM) induced an atropine- sensitive, two-to threefold increase in cellular levels of inositol 1, 4,5-trisphosphate, We examined the actions of LCT on binding of the ch olinergic radioligand [N-methyl-H-3]scopolamine ([H-3]NMS) to chief ce lls. Half-maximal inhibition of [H-3]NMS binding was observed with sim ilar to 0.5 mM carbachol and 1 mM LCT. These results indicate that the bile acid LCT is a partial agonist for muscarinic cholinergic recepto rs on gastric chief cells.