Role of cyclin-dependent kinase 5 in capsaicin-induced cough.
The role of cyclin-dependent kinase 5 (Cdk5) in the capsaicin-induced cough reflex was examined in mice. Pretreatment with inhaled roscovitine, a selective Cdk5 inhibitor, at concentrations of 0.3 to 3 mM inhibited the number of capsaicin-induced coughs in a concentration-dependent manner. Pretreatment with inhaled roscovitine, at a concentration of 3 mM also slightly but significantly inhibited the number of citric acid-induced coughs. The number of capsaicin-induced coughs was significantly reduced when C-fibers were desensitized by the pretreatment with capsaicin. The number of citric acid-induced coughs was slightly but significantly reduced in capsaicin-pretreated mice as compared with that in naive mice. Although the inhalation of roscovitine at a concentration of 3 mM significantly reduced the number of citric acid-induced coughs in naive mice to the level observed in capsaicin-pretreated mice, roscovitine had no effect on the number of citric acid-induced coughs in capsaicin-pretreated mice. These results suggest that Cdk5-dependent factors are involved in C-fiber-mediated cough signaling.
Kamei
Junzo
J
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan. kamei@hoshi.ac.jp
Hayashi
Shun-suke
SS
Takahashi
Yoshiki
Y
Nozaki
Chihiro
C
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D002211:Capsaicin; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D000077546:Roscovitine
D000996:Antitussive Agents; D047428:Protein Kinase Inhibitors; D011687:Purines; D000077546:Roscovitine; D019343:Citric Acid; D051360:Cyclin-Dependent Kinase 5; D002211:Capsaicin