Inhibition of glycine currents by dextromethorphan in neurones dissociated from the guinea-pig nucleus tractus solitarii.
1. The effect of dextromethorphan (DM) on the current induced by glycine in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea-pigs was studied by use of the whole-cell patch clamp technique. The effect of DM on gamma-aminobutyric acid (GABA)-induced currents (IGABA) was also examined. 2. DM inhibited 30 microM glycine-induced current (IGly), without affecting the current caused by 30 microM GABA. The action of DM was concentration-dependent, with a maximum effect at 100 microM, and reversible. The half-maximum inhibitory concentration (IC50) of DM was 3.3 microM, about 85 times higher than that of strychnine. 3. DM 3 microM shifted the concentration-response curve for glycine to the right without affecting the maximum value. DM 10 microM shifted the curve even more to the right, although it was not a parallel shift. Strychnine at a concentration of 0.1 microM shifted the curve for glycine in a nearly parallel fashion. 4. The effect of 10 microM DM was slightly weak voltage-dependency, but the lower concentration of DM, 3 microM, inhibited IGly equally at -50 mV and +50 mV. The effect of 3 microM DM on IGly showed no use-dependence. Blockade by strychnine 0.1 microM showed no voltage- or use-dependence. 5. The results indicate that DM inhibits IGly in single neurones of NTS, and further suggest that DM at a low concentration may act on the glycine receptor-ionophore complex, but not on the Cl channel of the complex. However, a relatively high concentration of DM may at least partly affect the Cl- channel of the complex.
Takahama
K
K
Department of Pharmacological Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Fukushima
H
H
Isohama
Y
Y
Kai
H
H
Miyata
T
T
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003915:Dextromethorphan / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006168:Guinea Pigs; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism; D013331:Strychnine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000996:Antitussive Agents; D005680:gamma-Aminobutyric Acid; D003915:Dextromethorphan; D013331:Strychnine; D005998:Glycine