Differential antagonism of airway contractile responses to prostaglandin (PG)D2 and 9 alpha, 11 beta-PGF2 by atropine, SK&F 88046 and SQ 29,548 in the guinea pig.

PGD2, the predominant prostanoid released from activated human lung mast cells, is metabolized to 9 alpha, 11 beta-PGF2 by an 11-ketoreductase. Both prostanoids contract mammalian airway smooth muscle. In the present study, aerosol administration of PGD2 or 9 alpha, 11 beta-PGF2 (five puffs of 10-50 micrograms/ml) to anesthetized, spontaneously breathing guinea pigs produced significant increases in airway resistance and decreases in dynamic lung compliance. The changes in airway resistance and dynamic lung compliance induced by 50 micrograms/ml were reduced approximately 60% and 25%, respectively, by pretreatment with atropine (1 mg/kg, i.v., -10 min). Pretreatment with the TxA2 receptor antagonist SK&F 88046 (N,N'-bis[7-(3-chlorobenzene aminosulfonyl)-1,2,3,4- tetrahydroisoquinolyl]disulfonylimide) (5 mg/kg, i.v., -10 min), nearly abolished the changes in airway resistance and dynamic lung compliance that were elicited by both agonists. Pretreatment with a TxA2 synthase inhibitor, CGS 13080 (10 mg/kg, i.v., -10 min), had no effect on PGD2- or 9 alpha, 11 beta-PGF2-induced bronchoconstriction, suggesting that these prostanoids did not provoke the release of TxA2. In vitro, PGD2, 9 alpha, 11 beta-PGF2 and a TxA2 mimic, U-44069, produced concentration-dependent contractions of the guinea pig isolated trachea with pD2s of 6.4, 6.0 and 7.2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)