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Postgraduate Studies in Pharmacology, University of Bradford, Bradford BD7 1DP and *The Royal Infirmary, Bradford BD9 6RJ1 Prostanoid receptors present on the pregnant human myometrium in vitro have been characterized according to the receptor classification proposed by Coleman et al. (1984) using natural prostanoids and synthetic, selective analogues and antagonists where available. 2 Prostaglandin E2 (PGE2) produced a biphasic effect consisting of an initial excitation followed by a dose-related inhibition. The EP2/EP3-receptor agonists, rioprostil and misoprostol, produced similar effects to PGE2, however, the excitatory event of the misoprostol response was related to dose. The EPI/EP3-receptor agonist, sulprostone, evoked a purely excitatory response which was unaffected by AH6809. The selective EP2-receptor agonist butaprost produced a long-lasting dose-dependent inhibition of activity. The results from these prostanoids indicated that inhibitory EP2-and excitatory EP3-receptors are present on myometrium from pregnant donors at term.3 PGF2,, and the synthetic FP-receptor agonist, fluprostenol, caused equipotent excitatory effects, indicating the presence of contractile FP-receptors. 4 PGD2 produced a biphasic effect of which the inhibition appeared dose-related and was antagonized by the selective DP-receptor antagonist BW A868C. The selective DP-receptor agonist, BW245C, produced a potent inhibitory effect that was competitively antagonized by BW A868C (pA2= 8.6).5 PGI2 produced a biphasic response qualitatively similar to PGE2. The EP,/IP-receptor agonist, iloprost, produced an occasional unquantifiable excitation and dose-related inhibition. The selective IP-receptor prostanoid, cicaprost, evoked only an inhibitory response. 6 The stable thromboxane A2 (TXA2)-mimetic, U46619, produced potent excitation which was competitively antagonized by the TP-receptor antagonist, GR32191 (pA2 = 7.2). 7 The prostanoids tested indicate that a heterogeneous population of prostanoid receptors are present on human myometrium from pregnant donors. It may be concluded that excitation is EP3-, FP-and TP-receptor-mediated and inhibition is EP2-, DP-and IP-receptor-mediated. Comparison of data obtained from non-pregnant specimens indicates that the lower segment tissue from pregnant donors demonstrated more pronounced responses to EP2 and IP-receptor activation.

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Postgraduate Studies in Pharmacology, University of Bradford, Bradford, BD7 lDP and *The Royal Infirmary, Bradford, BD9 6RJ1 Prostaglandin receptors of the PGE type have been characterized in the non-pregnant human myometrium in vitro according to the scheme of Coleman et al. (1984) by use of the agonists PGE2, sulprostone, rioprostil, AY23626, butaprost, misoprostol, 16,16-dimethylprostaglandin E2, enprostil and iloprost, and, the antagonist AH6809. 2 All prostanoids tested were active in non-pregnant human myometrium either as stimulators and/or inhibitors of spontaneous activity or both. Biphasic responses to PGE2 indicate that at least two receptor types of the EP-receptor exist, one mediating relaxation and the other mediating contraction. 3 Further evidence for the EP-receptor mediating excitation and relaxation was provided by the action of the EP2-/EP3-receptor selective prostanoids rioprostil, AY23626 and misoprostol, and the EP1-/EP2-receptor selective agonist 16,16-dimethylprostaglandin E2. 4 Butaprost, an EP2-receptor selective agonist, produced potent inhibition of spontaneous activity in the tissue which was generally longer-lasting than that evoked by the natural prostanoid PGE2. 5 The EP1-/EP3-receptor selective agonist sulprostone and the EP3-receptor agonist enprostil produced potent contractile responses supporting the presence of contractile EP3-receptors in the non-pregnant human myometrium in vitro.6 The EP,-/IP-receptor selective agonist, iloprost, produced mixed responses in non-pregnant human myometrium. The contractile response was inhibited by the EP,-receptor antagonist AH6809. However, responses to the EP1-/EP3-receptor selective agonist sulprostone were unaffected by AH6809 which may indicate that only a small population of EP1-receptors is present.

4 In preparations pre-constricted with phenylephrine (1 pM) both PGI2 and PGE2 were potent relaxant agonists. The selective IP-receptor agonists, cicaprost and iloprost, also dilated human uterine artery and were approximately 10 fold more potent than PG12. The EP2-receptor agonists, butaprost and rioprostil and the selective DP-agonist, BW 245C, were at least 100 fold weaker than PG12 and PGE2 suggesting that neither DP-nor EP2 receptors were involved. 5 We conclude that TP-receptors mediate constriction, whereas IP-and possibly EP4-receptors mediate relaxation of human uterine artery.