In vitro characterization of prostanoid EP‐receptors in the non‐pregnant human myometrium

Abstract

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.

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

“…Contractile EP 1 receptors do not have a widespread distribution in higher species and are more common in guinea pigs and murine species (Coleman et al, 1994b). In human tissues and cells, functional EP 1 receptors have been demonstrated in the myometrium (Senior et al, 1991), pulmonary veins (Norel et al, 2004), mast cells (Wang and Lau, 2006) colonic longitudinal muscle (Smid and Svensson, 2009), and keratinocytes (Konger et al, 2009).…”

Effect of the oestrous cycle, pregnancy and uterine region on the responsiveness of the isolated mouse uterus to prostaglandin F2α and the thromboxane mimetic U46619

“…The strips were attached to an isometric force transducer and a resting tension of 2 g (Chen et al 2001) was applied for superfusion with oxygenated Krebs (95% O 2 /5% CO 2 ) (Senior et al 1991) containing 1µM indometacin (Duckworth et al 2002) at 37 C. Tissues were left for 30 min to equilibrate.…”

Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

“…A wide range of agonists, including -adrenergic agents, and some prostaglandins, such as PGE 2 , are known to couple to receptors which elevate intracellular cAMP, and modifications in receptor density or G-protein-receptor coupling may assist in the maintenance of myometrial relaxation. For example, butaprost, an EP 2 -receptor selective agonist, provoked potent inhibition of spontaneous activity in samples of human myometrium (Senior et al 1991), and it has also been postulated that neuropeptides, such as calcitonin gene-related peptide, adrenomedullin and amylin, may act via G-protein linked receptors to contribute to the maintenance of uterine quiescence during human pregnancy (Casey et al 1997). Furthermore, the density of 2 -adrenoceptors, which positively couple to AC via G s, has been shown to decrease in human myometrium towards term (Litime et al 1989).…”