Influence Of Cisapride On Disordered Small-Bowel Motility In Intensive-Care Unit (Icu) Patients
GASTROENTEROLOGY(1995)
Abstract
5-HTla receptor agonists have been shown to antagonize cholinergica!!y mediated contractions by acting at 5-HTla receptors (Galligan, JPET, 260:306; 1992).However, in neuroblastoma ceils, where there are no 5-HTla receptors, agonists of this receptor prevent carbachol-stimulated breakdown of inositol phospholipid breakdown by acting at the rnuscadnic receptors (Fowler et al., Lif.Sci.48; 959,1991).The objective of this investigation was to determine if the motility effects are indeed mediated via 5-HT!a receptors or via muscarinic receptors, in vitro studies were conducted in rat colon longitudinal muscle-myenteric preparation (LM-MP).5-HT induced contractions were not antagonized by 8-OH DPAT, LY315535, and LY282073 potent 5-HTla agonists.Carbacholinduced contractions were antagonized by DPAT and LY315535 (EC50= 29.75 and 2.5 I~M, respectively).Potent 5-HTla antagonist had no effect on 5-HT or carbachol-induced contractions or on 5-HTla agonist-induced antagonism.LY282073 another potent and selective 5-HTla agonist, did not antagonize carbachol-induced contraction.In radioligand binding studies, LY315535 and LY282073 showed high affinity to the 5-HTla receptors ( IC50=0.2 and 0.4 nM, respectively).LY315535 and DPAT also showed binding affinity to muscarinic M1 receptors (IC50=160 and 1900 nM).LY282073 had no affinity to muscarinic receptors.In anesthetized rats LY315535 also inhibited carbachol-stimulated motility (ED50=0.8mglkg, i. v.).LY282073 and LY315535 were also evaluated in anesthetized ferrets.LY315535 inhibited spontaneous colonic motility potently (ED50=0.01mglkg, i. v.).LY282073 Was inactive at doses less than t mg/kg.The results of this study show that pharmacological agents, such as DPAT and LY315535, effect motility due to their affinity to muscarinic receptors, rather than 5-HTla receptors.Thus 5-HTta receptors may not play a direct significant role in modulation of gastrointestinal motility.
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Key words
small bowel motility,cisapride,intensive care unit,icu
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