The role of prostanoid TP‐ and DP‐receptors in the bronchoconstrictor effect of inhaled PGD 2 in anaesthetized guinea‐pigs: effect of the DP‐antagonist BW A868C

1 In anaesthetized, pump‐ventilated guinea‐pigs, bolus intravenous injection of prostaglandin D 2 (PGD 2 5–160 μg kg −1 ) caused a dose‐dependent rise in both heart rate and systemic mean arterial blood pressure with only a small monophasic rise in pulmonary inflation pressure (PIP). 2 In contrast, inhaled PGD 2 (0.1–1 mg ml −1 , 30s) provoked a substantial concentration‐dependent Diphasic rise in PIP. The bronchoconstrictor action of inhaled PGD 2 was accompanied by minimal cardiovascular effects. 3 The 3‐benzyl substituted hydantoin BW A868C (0.1–1 mg kg −1 i.v.) a novel prostanoid DP‐receptor antagonist, had no significant effect on the cardiovascular or bronchoconstrictor effects of intravenously administered or inhaled PGD 2 . 4 However, BW A868C (0.1–1 mg kg −1 i.v.) did inhibit the hypotensive actions of the DP‐receptor agonist, BW 245C (1–3 μg kg −1 i.v.). 5 The prostanoid TP‐receptor antagonist BM 13.177 (2.5 mg kg −1 i.v.) strongly inhibited the bronchoconstrictor effect of inhaled PGD 2 , abolishing the first phase of this response and reducing the peak increase in PIP provoked by PGD 2 (0.1 or 1 mg ml −1 for 30s), by 67 ± 16% and 44 ± 5% respectively. 6 A combination of BW A868C (0.1 or 1 mg kg −1 i.v.) with BM 13.177 (2.5 mg kg −1 i.v.) produced no greater inhibition of the bronchoconstrictor effect of inhaled PGD 2 than that seen with BM 13.177 (2.5 mg kg −1 i.v.) alone. 7 Neither bilateral vagotomy, nor selective inhibition of arachidonate cyclo‐oxygenase with indomethacin or 5‐lipoxygenase with the novel acetohydroxamic acid BW A4C, significantly reduced the bronchoconstrictor effect of inhaled PGD 2 . 8 These findings indicate that the bronchoconstrictor effect of inhaled PGD 2 in guinea‐pigs in vivo is mediated primarily through direct TP‐receptor activation and not through actions on DP‐receptors.