The terminals of myenteric intrinsic primary afferent neurons of the guinea-pig ileum are excited by 5-hydroxytryptamine acting at 5-hydroxytryptamine-3 receptors

The aim of this study was to identify the receptor type(s) by which 5-hydro xytryptamine applied to the intestinal mucosa excites the terminals of myen teric AH neurons. The AH neurons have been identified as the intrinsic prim ary afferent (sensory) neurons in guinea-pig small intestine and 5-hydroxyt ryptamine has been identified as a possible intermediate in the sensory tra nsduction process. Intracellular recordings were taken from AH neurons loca ted within 1 mm of intact mucosa to which 5-hydroxytryptamine was applied. Trains of action potentials and/or slow depolarizing responses were recorde d in AH neurons in response to mucosal application of 5-hydroxytryptamine ( 10 or 20 muM) or the 5-hydroxytryptamine-3 receptor agonist, 2-methyl-5-hyd roxytryptamine (1 or 3 mM), and to electrical stimulation of the mucosa. Th e 5-hydroxytryptamine-2 receptor agonist, alpha -methyl-5-hydroxytryptamine (100 muM), and the 5-hydroxytryptamine-1,2,4 receptor agonist, 5-methoxytr yptamine (10 muM), did not elicit such responses. The 5-hydroxytryptamine-3 receptor-selective antagonist, granisetron (typically 1 muM), and the 5-hy droxytryptamine-3,4 receptor antagonist, tropisetron (typically 1 muM), eac h reduced or abolished the responses to 5-hydroxytryptamine, while the sele ctive 5-hydroxytryptamine-4 receptor antagonist, SE 204070 (1 muM), did not . It is concluded that application of 5-hydroxytryptamine to the mucosa activ ates a 5-hydroxytryptamine-3 receptor that triggers action potential genera tion in the mucosal nerve terminals of myenteric AH neurons. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.