Effects of a thromboxane receptor antagonist on prostaglandin D2 and histamine induced bronchoconstriction in man

Abstract

Many prostanoids including are prostaglandin (PG) F2 alpha and PGD2 are potent bronchoconstrictor agents. There is evidence to suggest that airway thromboxane (TP) receptor may act as a common receptor for their bronchoconstrictor actions. We tested the hypothesis that inhaled prostaglandin (PG) D2-induced bronchoconstriction is mediated by interacting with the TP receptor antagonist, ICI 192605, on the bronchoconstrictor response to inhaled PGD2 in a double-blind, placebo-controlled and crossed-over trial in normal subjects. The effect of ICI 192605 on histamine induced bronchoconstriction served as control for non-specific bronchodilatory actions. The study had two phases; the first consisted of two inhaled PGD2 challenge study days, and the second phase was that of inhaled histamine. Each study day was separated by at least a week. On each study day, the challenge tests were carried out 30 min after ingestion of 100 mg ICI 192605 or placebo. Doubling concentrations of agonist were given till more than 35% fall in post-diluent specific airway conductance (sGaw) occurred. The concentration needed to cause a fall in a sGaw of 35% post-diluent value (PC35sGaw) was then determined from linear interpolation of the log dose-response. Eight male subjects (median age 26, range 20-35 years) completed the study. ICI 192605 did not change baseline airway calibre 30 min after ingestion on either PGD2 or histamine study days. ICI 192605 significantly shifted the dose-response curve to inhaled PGD2 to the right by a median of 3.4 fold (Wilcoxon rank sign test, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)