Abstract
Interaction between the 5-HT 4 receptor and cholinergic-dependent and -independent contraction of the rat oesophageal muscularis mucosae was determined. Substance P- (in the presence of atropine) and carbachol-precontracted tissue was relaxed by tryptamines and the substituted benzamides with the following rank order of potency: 5-HT>5-methoxytryptamine>cisapride>( R)-zacopride>lintopride>metoclopramide, consistent with 5-HT 4 receptor activation. The response to 5-HT was not antagonized by tetrodotoxin, methysergide or ondansetron, but was shifted to the right by GR113808 ([1-[2-[methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-1- H-indole-3-carboxylate) in substance P- and carbachol-precontracted tissue, confirming 5-HT 4-mediated relaxation. This study shows for the first time that although 5-HT 4 receptors are involved in the modulation of cholinergic neurotransmission they can also act independently of this system modulating tachykinergic responsiveness. © 1997 Elsevier Science B.V. All rights reserved.
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