In vitro characterization of prostanoid receptors on human myometrium at term pregnancy

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Abstract
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. 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 EP1/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. PGF2α and the synthetic FP‐receptor agonist, fluprostenol, caused equipotent excitatory effects, indicating the presence of contractile FP‐receptors. 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). PGI2 produced a biphasic response qualitatively similar to PGE2. The EP1/IP‐receptor agonist, iloprost, produced an occasional unquantifiable excitation and dose‐related inhibition. The selective IP‐receptor prostanoid, cicaprost, evoked only an inhibitory response. The stable thromboxane A2 (TXA2)‐mimetic, U46619, produced potent excitation which was competitively antagonized by the TP‐receptor antagonist, GR32191 (pA2 = 7.2). 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.