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Lithocholyltaurine interacts with cholinergic receptors on dispersed chief cells from guinea pig stomach
J P Raufman1, P Zimniak, A Bartoszko-Malik
1Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205-7199, USA.
Abstract:
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.
Insights
The bile acid lithocholyltaurine (LCT) acts as a partial agonist on gastric chief cells, affecting pepsinogen secretion. This finding helps explain how bile acids damage the gastric mucosa.
Area of Science:
- Gastroenterology
- Cell Biology
- Pharmacology
Background:
- Bile acids are known to damage gastric mucosa, but the precise mechanisms remain unclear.
- Gastric chief cells secrete pepsinogen, a key component of gastric function and a target for injury.
Purpose of the Study:
- To investigate the effects of various bile acids on gastric chief cell secretory function.
- To determine if bile acids interact with cholinergic pathways in gastric chief cells.
Main Methods:
- Primary cultures of gastric chief cells were used to assess pepsinogen secretion.
- Bile acid actions were tested in combination with other secretagogues like carbachol and CCK.
- Cholinergic receptor binding assays and inositol trisphosphate measurements were performed.
Main Results:
- Lithocholyltaurine (LCT), a specific bile acid conjugate, significantly increased pepsinogen secretion.
- LCT demonstrated partial cholinergic agonist activity, inhibiting carbachol-stimulated secretion.
- LCT binding to muscarinic cholinergic receptors was observed, similar to carbachol.
Conclusions:
- The bile acid LCT functions as a partial agonist at muscarinic cholinergic receptors on gastric chief cells.
- This interaction with cholinergic receptors contributes to the understanding of bile acid-induced gastric mucosal injury.