Characterization of contractile prostanoid receptors on human airway smooth muscle

In human bronchial rings the thromboxane A2 (TxA2) mimetic, U46619, produced cumulative concentration-related contractions up to a maximum of 141 +/- 23% of the response induced by carbachol or acetylcholine. The geometric mean EC50 value was 3.2 X 10(-8) M (95% confidence interval: 1.2, 8.9 X 10(-8) M) (n = 5). Contractions to U46619 were unaffected by atropine (10(-6) M) or verapamil (10(-5) M), but were competitively antagonized by the TxA2 antagonist GR32191 with a pA2 value of 8.40 +/- 0.41. The maximum contractile response to prostaglandin (PG) F2 alpha was smaller (90 +/- 9%, n = 13) and the potency was less (EC50 = 2 X 10(-6) M) than that of U46619. Contractions to PGF2 alpha were also competitively antagonized by GR32191 with a pA2 value of 8.18 +/- 0.08. Concentration-response curves to PGE2 were biphasic, relaxation at concentrations from 10(-9) to 10(-6) M and contraction from 10(-6) to 3 X 10(-5) M. GR32191 10(-7) M inhibited the contractile portion of the response curve in 8 of 11 tissues. Based on these results we conclude that U46619, PGF2 alpha and PGE2 all contract human airways by stimulation of the TxA2 (TP) receptor.