Inhibition of the serotonin-induced inward current by dextromethorphan in rat nodose ganglion neurons

Hitoshi Ishibashi, Kei Eto, Yukiko Arimura, Jun Yamada, Yoshiko Hatano, Masazumi Nishikawa, Mami Noda, Kazuo Takahama

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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-HT3 receptor antagonist tropisetron, while the selective 5-HT3 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 IC50 values for the inhibition of peak and steady currents evoked by 3 μM 5-HT were 16.4 and 34.4 μM, respectively. In the presence of 10 μM 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 EC50 values in the presence of 0, 10, 30 and 60 μM dextromethorphan were 4.3, 6.8, 15.5 and 40.6 μM, 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-HT3 receptors.

Original languageEnglish
Pages (from-to)65-70
Number of pages6
JournalBrain Research
Volume1097
Issue number1
DOIs
Publication statusPublished - Jun 30 2006

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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