Inhibition of the Serotonin-induced Inward Current by Dextromethorphan in Rat Nodose Ganglion Neurons.
From: 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
Brain research
- Publish Date: Jun 2006
- ISSN: 0006-8993
- Volume: 1097
- Issue: 1
- Pages: 65-70
- Medium: Print
- Language: English
- Citation (JAMA): Ishibashi Hitoshi, Eto Kei, Arimura Yukiko, et al. Inhibition of the Serotonin-induced Inward Current by Dextromethorphan in Rat Nodose Ganglion Neurons.. Brain Res. Jun 2006;1097:65-70
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.
Mesh Headings (Keywords): Animals, Cells, Cultured, Dextromethorphan, Dose-Response Relationship, Drug, Neural Inhibition, Neurons, Nodose Ganglion, Rats, Rats, Wistar, Serotonin
Check for Full Text / PubMed Unique Identifier (PMID): 16730674
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