Pharmacological characterization of prostanoid receptors present in the porcine uterus

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In the present research project, prostanoid receptor subtype and distribution of cyclooxygenase (COX) in the porcine uterus were characterized using pharmacological and biochemical techniques, and physiological roles of prostanoid in regulation of myometrial contractility were discussed. Contractile (EP1, EP3, FP and TP) and relaxant prostanoid receptors (DP, IP and EP2) were demonstrated in the porcine uterus muscle and these receptor populations were consistent with human. Therefore the porcine uterus might be a useful animal model for assessing the mechanical actions of prostanoid receptor agonists in the human uterus. Prostanoid receptors in the porcine uterus was suggested to distribute heterogeneously depending on smooth muscle types (longitudinal and circular muscle) and uterine regions (cornu, corpus and cervix). In the longitudinal muscle, responsiveness to contractile prostanoid receptor agonists was high compared with the circular muscle and decreased gradually from cornu to … More cervix. In contrary, responsiveness to relaxant prostanoid receptor agonists was low in the cornu and increased toward cervix. On the other hand, although responses to relaxant prostanoid receptor agonists were high in the circular muscle, regional difference in responsiveness to both contractile and relaxant prostanoid receptor agonists was not marked in comparison with the case of longitudinal muscle. The heterogeneous distribution of contractile and relaxant prostanoid receptor contributes to produce a gradient of the intra-luminal pressure from the cornu (high) to cervix (low) that is convenient for transportation of luminal contents. COX-1 but not COX-2 was expressed in the non-pregnant porcine uterus and distributed heterogeneously depending on muscle layer and uterine regions as did contractile prostanoid receptors. Inhibitors of COX and thromboxane A2 synthase decreased the spontaneous contraction of longitudinal muscle but not circular muscle. Present results suggest that prostanoid modulates, spontaneous myometrial contractility in pig. In the uterus of pregnant pig, COX-2 was expressed intensely and the responsiveness to a FP receptor agonist increased, suggesting a pregnancy-associated change in the physiological role of COX-prostanoid pathway. Further examinations might be necessary to clarify how steroid hormones regulate prostanoid receptor and COX expression, and myometrial motility. Less