Pharmacological characterization of prostanoid receptors present in the porcine uterus

本研究利用药理学和生物化学技术研究了猪子宫环氧合酶(COX)的前列腺素受体亚型和分布，并探讨了前列腺素在调节子宫肌层收缩中的生理作用。收缩(EP1、EP3、FP和TP)和舒张性前列腺素受体(DP、IP和EP2)存在于猪子宫肌内，这些受体与人的一致。因此，猪子宫可能是评估前列腺素受体激动剂在人子宫中的机械作用的有用的动物模型。猪子宫的前列腺素受体分布不均，这取决于子宫的平滑肌类型(纵肌和环肌)和子宫区域(角、体部和子宫颈)。在纵肌中，收缩前列腺素受体激动剂的反应性比环肌高，并且从角部到…逐渐降低更多的宫颈。相反，松弛的前列腺素受体激动剂在角部的反应性较低，而对宫颈的反应性增加。另一方面，尽管环状肌对松弛前列腺素受体激动剂的反应性很高，但与纵行肌相比，收缩和松弛前列腺素受体激动剂的反应性没有明显的区域性差异。收缩和松弛前列腺素受体的异质性分布有助于产生腔内压力从角部(高)到宫颈(低)的梯度，这有利于腔内容物的运输。COX-1在非妊娠猪子宫中表达，但不表达COX-2，其分布取决于肌层和子宫区域，收缩前列腺素受体也是如此。COX和血栓素A2合成酶的抑制剂减少纵肌的自发收缩，但不减少环行肌的自发收缩。目前的研究结果表明，前列腺素对猪子宫肌自发性收缩有调节作用。在妊娠猪的子宫中，COX-2表达强烈，对FP受体激动剂的反应性增强，提示COX-前列腺素途径的生理作用与妊娠相关。进一步的检查可能需要阐明类固醇激素如何调节前列腺素受体和环氧合酶的表达，以及子宫肌层的运动。较少

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