Pharmacological characterization in vitro of prostanoid receptors in the myometrium of nonpregnant ewes

Prostanoid receptors regulating the contractility of strips of myometrium obtained from nonpregnant ewes during the breeding season were classified pharmacologically. Natural prostanoids, receptor-type selective synthetic analogues, and selective antagonists were used where available. The natural prostanoids PGD2, PGE2, and PGF2 alpha were equipotent in causing contractions (pD2 values of 6.9, 6.7, and 6.9, respectively) but were 100 times less potent than oxytocin (pD2 = 9.2). The synthetic prostanoids iloprost (pD2 = 8.3), GR63799x (pD2 = 7.0), cloprostenol (pD2 = 6.8), and U46619 (pD2 = 6.2) also caused contractions. The effects of iloprost, but not of GR63799x, were blocked by the selective EP1 antagonist AH 6809. This suggests the presence of both EP1 and EP3 receptors. The similar potencies of cloprostenol and PGF2 alpha suggest the presence of FP receptors. Although the potency of the TP agonist U46619 was relatively low, its effects were blocked by the selective TP antagonist L 670596 (pKB = 8.4), an observation consistent with the presence of TP receptors. Thus, all currently recognized excitatory prostanoid receptors (EP1, EP3, FP and TP) appeared to be present. Contractions induced by cloprostenol and KCl could be inhibited by the beta-adrenoceptor agonist isoprenaline (pD2 = 8.8 against cloprostenol) and the Ca(2+)-channel blocker, D600 (pD2 = 6.3 against cloprostenol), but a number of relaxant prostanoids, BW245c, ZK110841, AH13205 and cicaprost, could not produce inhibition. These results suggest that DP, EP2 and IP receptors do not regulate contractility under these conditions.