Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT4 agonist--tegaserod

BMC Gastroenterology
Ronald Mathison, Eldon Shaffer

Abstract

Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT4 receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. The effects of a high cholesterol (1%) diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX). Two groups of animals, fed either low (0.03%) or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. The high cholesterol diet increased, by nearly ...Continue Reading

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Citations

Nov 10, 2012·World Journal of Gastroenterology : WJG·Da-Peng ChenYuan Lin
Mar 29, 2012·Canadian Journal of Physiology and Pharmacology·Dapeng ChenYuan Lin
Oct 1, 2013·Pharmaceutical Biology·Dapeng ChenYuan Lin
Apr 23, 2013·The Journal of Pharmacy and Pharmacology·Da-Peng ChenYuan Lin

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