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 24 h after an antigen challenge in actively sensitized guinea pigs, and then bronchoalveolar lavage (BAL) was performed. Olprinone (1 or 10 mg/kg) or SB207499 (1 or 10 mg/kg) was given twice intraperitoneally: One hour after the antigen challenge and 1 h 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.