The antitussive effect of cromakalim in rats is not associated with adenosine triphosphate sensitive K+ channels.
The effects of cromakalim, a K+ channel opener, on the capsaicin-induced cough reflex in rats were studied. I.P. administration of cromakalim in doses of 0.1 to 1.0 mg/kg decreased the number of induced coughs in a dose- dependent manner. Neither glibenclamide, an adenosine triphosphate-sensitive K+ channel blocker, nor tetraethylammonium, a blocker of other types of K+ channels, affected the antitussive effect of cromakalim. However, the antitussive effect of cromakalim was antagonized by methysergide, a 5-HT antagonist. Although Bay K 8644, a dihydropyridine Ca2+ channel activator, had a marked cough-depressant effect, it had no effect on the antitussive effect of cromakalim. These results suggest that the antitussive effect of cromakalim is primarily mediated by activation of the serotonergic system through the inhibition of voltage-dependent Ca2+ channels, and not through the activation of K+ channels.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
J
J
Kamei
Y
Y
Iwamoto
M
M
Narita
T
T
Suzuki
M
M
Misawa
Y
Y
Kasuya
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000996:Antitussive Agents; D001578:Benzopyrans; D015220:Calcium Channels; D015221:Potassium Channels; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; D019806:Cromakalim; D000255:Adenosine Triphosphate; D002211:Capsaicin; D005905:Glyburide; D008784:Methysergide