Cholinergic-mediated bronchoconstriction induced by prostaglandin D2, its initial metabolite 9 alpha,11 beta-PGF2, and PGF2 alpha in asthma.
In this study, we have investigated the contribution of cholinergic-mediated bronchoconstriction in the airway response provoked by inhaled prostaglandin (PG)D2, its metabolite 9 alpha, 11 beta-PGF2, and PGF2 alpha, which are generated during mast cell activation in vivo and are potent bronchoconstrictor agonists in humans. The effect of prior inhalation of 1 mg ipratropium bromide (IB) on the bronchoconstrictor response to inhaled methacholine (MCh), PGD2, 9 alpha, 11 beta-PGF2, and PGF2 alpha was determined in 7 allergic asthmatic subjects by measuring changes in SGaw, FEV1, and Vmax30. Methacholine, PGD2, and 9 alpha, 11 beta-PGF2 caused concentration-related bronchoconstriction with PGD2 and 9 alpha, 11 beta-PGF2 being between 45 and 112 times more potent than MCh (p less than 0.05), depending on the method used to measure airway caliber. Preinhalation of IB displaced the concentration response curves to MCh between 69- and 196-fold to the right, and this was significantly greater than that observed with PGD2 (12- to 23-fold, p less than 0.02) and 9 alpha, 11 beta-PGF2 (12- to 22-fold, p less than 0.02). Ipratropium bromide inhibited the bronchoconstriction achieved with the highest concentration of agonist by 73 to 91% with MCh, 46 to 79% with PGD2, and 32 to 38% with 9 alpha, 11 beta-PGF2. Ipratropium bromide did not affect the bronchoconstriction pattern to inhaled PGF2 alpha, irrespective of the nature of the response. We conclude that although PGD2 and 9 alpha, 11 beta-PGF2 are potent contractile agonists of human smooth muscle in vitro, bronchoconstriction observed with these mediators in vivo results from a combination of both direct and cholinergic-mediated mechanisms.
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects / Q000294:innervation*; D015237:Dinoprost; D005540:Forced Expiratory Flow Rates; D005541:Forced Expiratory Volume; D006801:Humans; D009241:Ipratropium / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000494:pharmacology*; D011457:Prostaglandins D / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology
D008688:Methacholine Compounds; D011453:Prostaglandins; D011457:Prostaglandins D; D011460:Prostaglandins F; D016210:Methacholine Chloride; D015237:Dinoprost; D009241:Ipratropium; D015230:Prostaglandin D2