Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs.
Effects of the selective phosphodiesterase 3 (PDE3) inhibitor olprinone and the selective PDE4 inhibitor SB207499 were investigated on antigen-induced increase of cough reflex sensitivity and normal cough response to capsaicin in guinea pigs. Number of coughs elicited by inhalation of capsaicin (10(-8), 10(-6) and 10(-4)M) was counted 24h after an antigen challenge in actively sensitized guinea pigs, and then bronchoalveolar lavage (BAL) was performed. Olprinone (1 or 10mg/kg) or SB207499 (1 or 10mg/kg) was given twice intraperitoneally: One hour after the antigen challenge and 1h before the capsaicin provocation. SB207499, but not olprinone, significantly reduced both antigen-induced increase of cough response to inhaled capsaicin in sensitized animals and normal cough response in non-sensitized animals. SB207499, but not olprinone, also reduced the antigen-induced BAL eosinophilia. PDE4 inhibitors may be useful in treating cough associated with airway allergy via inhibiting both allergic airway inflammation and the common pathway of cough reflex.
Fujimura
Masaki
M
Respiratory Medicine, Cellular Transplantation Biology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan. fujimura@med3.m.kanazawa-u.ac.jp
Liu
Qi
Q
D000485:Allergens; D000818:Animals; D000941:Antigens; D018893:Bronchoalveolar Lavage; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000188:drug therapy; D006168:Guinea Pigs; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D007274:Injections, Intraperitoneal; D008297:Male; D009570:Nitriles; D058987:Phosphodiesterase 3 Inhibitors; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects
D000485:Allergens; D000941:Antigens; D003509:Cyclohexanecarboxylic Acids; D007093:Imidazoles; D009570:Nitriles; D058987:Phosphodiesterase 3 Inhibitors; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C059498:olprinone; C433247:Cilomilast; D002211:Capsaicin