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-hydroxytryptamine applied to the intestinal mucosa excites the terminals of myenteric AH neurons. The AH neurons have been identified as the intrinsic primary afferent (sensory) neurons in guinea-pig small intestine and 5-hydroxytryptamine has been identified as a possible intermediate in the sensory transduction process. Intracellular recordings were taken from AH neurons located within 1mm of intact mucosa to which 5-hydroxytryptamine was applied. Trains of action potentials and/or slow depolarizing responses were recorded in AH neurons in response to mucosal application of 5-hydroxytryptamine (10 or 20microM) or the 5-hydroxytryptamine-3 receptor agonist, 2-methyl-5-hydroxytryptamine (1 or 3mM), and to electrical stimulation of the mucosa. The 5-hydroxytryptamine-2 receptor agonist, alpha-methyl-5-hydroxytryptamine (100microM), and the 5-hydroxytryptamine-1,2,4 receptor agonist, 5-methoxytryptamine (10microM), did not elicit such responses. The 5-hydroxytryptamine-3 receptor-selective antagonist, granisetron (typically 1microM), and the 5-hydroxytryptamine-3,4 receptor antagonist, tropisetron (typically 1microM), each reduced or abolished the responses to 5-hydroxytryptamine, while the selective 5-hydroxytryptamine-4 receptor antagonist, SB 204070 (1microM), did not. It is concluded that application of 5-hydroxytryptamine to the mucosa activates a 5-hydroxytryptamine-3 receptor that triggers action potential generation in the mucosal nerve terminals of myenteric AH neurons.
Bertrand
P P
PP
Department of Physiology, University of Melbourne, Victoria 3010, Parkville, Australia. P.Bertrand@physiology.unimelb.edu.au
Kunze
W A
WA
Furness
J B
JB
Bornstein
J C
JC
D008735:5-Methoxytryptamine / Q000378:metabolism / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D017829:Granisetron / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077526:Tropisetron
D008735:5-Methoxytryptamine; D004146:Dioxanes; D017829:Granisetron; D007211:Indoles; D010880:Piperidines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D000077526:Tropisetron; C084858:SB 204070A; C042390:alpha-methylserotonin; C045918:2-methyl-5-HT