Differential Antagonism of Airway Contractile Responses to Prostaglandin (PG)D2 and 9a,1 1f3-PGF2 by Atropine, SK&F 88046 and SQ 29,548 in the Guinea Pig

PGD2, the predominant prostanoid released from activated hu-man lung mast cells, is metabolized to 9a,1 1 f3-PGF2 by an 11-ketoreductase. Both prostanoids contract mammalian airway smooth musde. In the present study, aerosol administration of PGD2 or 9a,1 1 fl-PGF2 (five puffs of 10-50,g/ml)to anesthetized, spontaneously breathing guinea pigs produced significant in-creases in airway resistance and decreases in dynamic lung compliance. The changes in airway resistance and dynamic lung compliance induced by 50,g/ml were reduced approximately 60 % and 25%, respectively, by pretreatment with atropine (1 mg/kg, i.v.,-1 0 mm). Pretreatment with the TxA2 receptor antagonist SK&F 88046 (N,N’-bis[7-(3-chlorobenzene aminosul-fonyl)-1,2,3,4-tetrahydroisoquinolyl]disulfonylimide) (5 mg/kg, i.v.,-1 0 mm), nearly abolished the changes in airway resistanc