TY - JOUR T1 - Acute Experimental Esophagitis Activates a Second Signal Transduction Pathway in Cat Smooth Muscle from the Lower Esophageal Sphincter JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1293 LP - 1304 VL - 283 IS - 3 AU - U. D. Sohn AU - K. M. Harnett AU - W. Cao AU - H. Rich AU - N. Kim AU - J. Behar AU - P. Biancani Y1 - 1997/12/01 UR - http://jpet.aspetjournals.org/content/283/3/1293.abstract N2 - In single cells, isolated by enzymatic digestion from the circular muscle layer of the lower esophageal sphincter (LES), acute experimental esophagitis (AE) alters signal transduction in response to a maximally effective dose of acetylcholine. In normal LES contraction was inhibited by M3 ≫ M1 or M2antagonists. In AE inhibition by M2 antagonists increased significantly so that contraction was inhibited by M3 > M2 > M1 antagonists. In normal cells permeabilized by saponin, contraction was antagonized by antibodies against Gq/11, by the phosphatidylinositol-specific phospholipase C (PI-PLC) antagonist U 73122, but not by the phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor D609, or by the phospholipase D pathway inhibitor propranolol. In AE contraction was reduced by Gq/11 and Gi3antibodies and by U73122, propranolol and D609. After thapsigargin treatment of normal cells to reduce intracellular Ca++stores, contraction was inhibited by M2 and M3antagonists, by antibodies against Gq/11 and Gi3, by U73122, D609 and propranolol, suggesting that depletion of Ca++ stores reproduces the changes induced by AE. We conclude that in normal LES smooth muscle cells acetylcholine-induced contraction is mediated by M3receptors linked to Gq/11 and PI-PLC, whereas in AE, contraction through this pathway is reduced, perhaps because of reduction in Ca++ stores, and a second pathway is activated by M2 receptors linked to Gi3, PC-PLC and phospholipase D. The American Society for Pharmacology and Experimental Therapeutics ER -