TY - JOUR
T1 - Inhibition of the serotonin-induced inward current by dextromethorphan in rat nodose ganglion neurons
AU - Ishibashi, Hitoshi
AU - Eto, Kei
AU - Arimura, Yukiko
AU - Yamada, Jun
AU - Hatano, Yoshiko
AU - Nishikawa, Masazumi
AU - Noda, Mami
AU - Takahama, Kazuo
N1 - Funding Information:
We thank Dr. A. Moorhouse for discussion and editing of the manuscript. This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2006/6/30
Y1 - 2006/6/30
N2 - 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.
AB - 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.
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U2 - 10.1016/j.brainres.2006.04.036
DO - 10.1016/j.brainres.2006.04.036
M3 - Article
C2 - 16730674
AN - SCOPUS:33745909436
SN - 0006-8993
VL - 1097
SP - 65
EP - 70
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1
ER -