Are glycine receptors a possible target for cough potentiating agents?

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.30-30
• Main Authors: Kazuo Takahama, Hidenao Fukushima, Fumio Soeda, Shin-ichi Nagayama, Takeshi Miyata, Aki Kato, Hitoshi Ishibashi
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Based on several lines of evidence, our attention has been focused on a possible role of glycine receptors in cough reflex mechanisms in the brain stem. In this study, we examined whether or not glycinergic transmission exists in the NTS, and then studied the effect of antitussives and related substances on the glycine-induced currents (I_gly ) in NTS neurons of guinea-pigs. Method Transverse slices (200-250 μm in thickness) were prepared from 6-9 days-old Hartley guinea-pigs. The NTS neurons were acutely dissociated from 7-10 days-old Hartley guinea-pigs. The postsynaptic and the membrane currents were recorded by using a whole cell patch-clamp technique. All substances were applied in the perfusate or by a Y-tube technique. Results One of three types of postsynaptic currents recorded in the NTS was strychnine-sensitive. Dextromethorphan (DM) at concentrations of 1-100 μM inhibited I_gly , whereas codeine and morphine at concentrations of 10-1000 μM did so. The inhibitory effect showed little voltage- and use-dependency. Interestingly, newly synthesized substances, possessing a morphan structure which is a part of chemical structures of the antitussives used, potentiated I_gly in NTS neurons. Taking the results together with the cumulated findings, pharmacological significance of glycine receptors in the NTS will be discussed.