Lithocholyltaurine interacts with cholinergic receptors on dispersed chief cells from guinea pig stomach.
Although bile acids damage gastric mucosa, the mechanisms underlying tissue injury induced by these agents are not well understood. To determine whether bile acids alter gastric secretory function, we investigated the actions of sodium cholate, deoxycholate, lithocholate, and their taurine and glycine conjugates on a highly homogeneous population of gastric chief cells. Lithocholyltaurine (LCT), a particularly injurious bile acid, caused a threefold increase in pepsinogen secretion (detectable with 100 nM and maximal with 10 microM LCT). When combined with other secretagogues, increasing concentrations of LCT caused progressive inhibition of carbamylcholine (carbachol)-induced pepsinogen secretion 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 cholinergic agonist. To test this hypothesis, we examined the actions of the cholinergic antagonist atropine on LCT-induced pepsinogen secretion. Atropine (10 microM) abolished carbachol- and LCT-induced pepsinogen secretion. 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 cholinergic radioligand [N-methyl-3H]scopolamine ([3H]NMS) to chief cells. Half-maximal inhibition of [3H]NMS binding was observed with approximately 0.5 mM carbachol and 1 mM LCT. These results indicate that the bile acid LCT is a partial agonist for muscarinic cholinergic receptors on gastric chief cells.
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205-7199, USA.
J P
JP
Raufman
P
P
Zimniak
A
A
Bartoszko-Malik
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D019872:Chief Cells, Gastric / Q000502:physiology*; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D019832:N-Methylscopolamine / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology; D010435:Pepsinogens / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000502:physiology*; D012844:Sincalide / Q000378:metabolism; D013658:Taurolithocholic Acid / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D010276:Parasympatholytics; D010435:Pepsinogens; D011950:Receptors, Cholinergic; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013658:Taurolithocholic Acid; D001285:Atropine; D002217:Carbachol; D002766:Cholecystokinin; D012844:Sincalide; D019832:N-Methylscopolamine