title: Inhibition of the serotonin-induced inward current by dextromethorphan in rat nodose ganglion neurons.
abstract: Dextromethorphan is one of the most widely used antitussives for the treatment of cough. In the present study, we investigated the effect of dextromethorphan on 5-hydroxytryptamine (5-HT)-induced currents in acutely dissociated rat nodose ganglion neurons using nystatin-perforated patch-clamp recording configuration. The 5-HT-induced current was inhibited by the 5-HT(3) receptor antagonist tropisetron, while the selective 5-HT(3) receptor agonist 1-(m-chlorophenyl)-biguanide hydrochloride (mCPBG) induced a similar current. Dextromethorphan reversibly and concentration-dependently inhibited the 5-HT-induced inward current. The inhibition did not appear to be voltage-dependent. Both the peak and steady-state 5-HT-induced currents were inhibited by dextromethorphan, although the peak current was more sensitive to dextromethorphan block. The IC(50) values for the inhibition of peak and steady currents evoked by 3 muM 5-HT were 16.4 and 34.4 muM, respectively. In the presence of 10 muM dextromethorphan, the concentration-response curve for 5-HT was shifted to the right without changing the maximum response, while high concentrations reduced the maximum current. The 5-HT EC(50) values in the presence of 0, 10, 30 and 60 muM dextromethorphan were 4.3, 6.8, 15.5 and 40.6 muM, respectively. The results indicate that dextromethorphan inhibits the 5-HT-induced current of rat nodose ganglion neurons, and further suggest that dextromethorphan at a low concentration acts as a competitive inhibitor of 5-HT(3) receptors.
authors.affiliation: Department of Bio-signaling Physiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka-City 812-8582, Japan. h-ishi@physiol2.med.kyushu-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Kei
authors.initials: K
authors.lastname: Eto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Arimura
authors.forename: Jun
authors.initials: J
authors.lastname: Yamada
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hatano
authors.forename: Masazumi
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahama
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003915:Dextromethorphan / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009620:Nodose Ganglion / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*
chemical_list: D012701:Serotonin; D003915:Dextromethorphan