title: Functional roles of 5-hydroxytryptamine 3/4 receptors in neurons of rat dorsal motor nucleus of the vagus.
abstract: In neurons of dorsal motor nucleus of the vagus that is involved in the gastric motility and possibly emesis, application of 5-hydroxytryptamine produces membrane depolarization, and suppresses spike-repolarization and spike-afterhyperpolarization, suggesting divergent effects of 5-hydroxytryptamine through activating multiple subtypes of 5-hydroxytryptamine receptors. However, only the role of 5-hydroxytryptamine 2A receptors has been established to be responsible for the depolarization, and the mechanisms underlying the modulation of spikes remain unknown although a role of 5-hydroxytryptamine 4 receptors was implicated in modulations of spikes. There is now increasing evidence for the role of 5-hydroxytryptamine receptors in neurons involved in generating emesis following administration of anticancer drug. Since antagonists of 5-hydroxytryptamine 3/4 receptors are widely used as anti-emetic drugs, we have reevaluated the functional roles of 5-hydroxytryptamine 3/4 receptors of dorsal motor nucleus of the vagus neurons, especially in modulating transient outward currents that are presumed to be involved in spike-repolarization and spike-afterhyperpolarization. Whole-cell patch-clamp recordings were made from the dorsal motor nucleus of the vagus neurons, which were identified by a retrograde tracing method with dextran-tetramethylrhodamine-lysine injected into a bundle of abdominal vagus nerves. Under a voltage-clamp condition, dorsal motor nucleus of the vagus neurons expressed a prominent A-like current. The activation of 5-hydroxytryptamine 3 receptors reversibly increased the resting membrane conductance while the activation of 5-hydroxytryptamine 4 receptors led to an almost irreversible decrease in the A-like current. A long-lasting suppression of A-like current by transient activation of 5-hydroxytryptamine 4 receptors would result in a long-lasting increase in the excitability of dorsal motor nucleus of the vagus neurons, which might be involved in generation of the long-lasting facilitation of gastric motility or in generation of the long-lasting gastric relaxation through the activation of enteric non-adrenergic non-cholinergic neurons as implicated in the delayed emesis induced by anticancer drugs.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Fukushi
authors.affiliation: Department of Neuroscience and Oral Physiology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Neuroscience and Oral Physiology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Endo
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hamaue
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirafuji
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Minami
authors.affiliation: Department of Neuroscience and Oral Physiology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: kang@dent.osaka-u.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
mesh_terms: D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D017829:Granisetron / Q000494:pharmacology; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*; D062366:para-Aminobenzoates
chemical_list: D010129:4-Aminobenzoic Acid; D008735:5-Methoxytryptamine; D002118:Calcium; D017829:Granisetron; D044406:Receptors, Serotonin, 5-HT3; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D062366:para-Aminobenzoates; C072790:2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester; C045918:2-methyl-5-HT