title: 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)
authors.affiliation: Department of Thoracic Medicine, London Chest Hospital.
authors.forename: N
authors.initials: N
authors.lastname: al Jarad
authors.forename: K P
authors.initials: KP
authors.lastname: Hui
authors.forename: N
authors.initials: N
authors.lastname: Barnes
mesh_terms: D000328:Adult; D016084:Bronchoconstriction / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology*; D004311:Double-Blind Method; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D015230:Prostaglandin D2 / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012907:Smoking
chemical_list: D004146:Dioxanes; D017482:Receptors, Thromboxane; C057498:ICI 192605; D006632:Histamine; D015237:Dinoprost; D015230:Prostaglandin D2