The mechanism of initiation of labor in human.

我们之前的研究表明，多巴胺对人蜕膜组织产生前列腺素具有抑制作用，这支持了羊水多巴胺与人类分娩的开始或维持有关的假设。在本研究中，我们利用多巴胺DA-1受体配体[^3H]SCH23390证明了多巴胺DA-1受体的存在。平衡解离常数（Kd）为1.87 nM，最大结合容量（Bmax）为79.0 fmol/mg蛋白。利用已知与DA-1受体相互作用的药物和已知与DA-2受体和β -肾上腺素能受体相互作用的药物进行的竞争性实验表明，[^3H]SCH23390的高亲和力结合位点是DA-1受体。磷脂酶A_2 （PLA_2）被认为是PG生产的限速步骤。近年来，已检测到PLA_2的几种同工型。胞质85 kD异构体，称为胞质PLA_2 (cPLA_2)，被认为通过受体刺激释放花生四烯酸合成PG。本研究对人羊膜和蜕膜细胞质组分中的PLA_2进行了sn-2脂肪酸特异性和凝胶过滤层析分析。花生四烯酸与油酸的释放比羊膜为2.12，蜕膜为2.06。凝胶-过滤层析表明，其分子量约为85 kD。结果表明该酶与cPLA_2相对应，并观察了羊膜和蜕膜中cPLA_2活性的变化。阴道分娩时，蜕膜活性明显低于分娩前。从这些结果来看，我们认为人蜕膜中通过多巴胺受体产生的前列腺素可能参与了分娩的开始。

Our previous study that dopamine has a stumilatory effect on prostaglandin production by human decidual tissue supports the hypothesis that amniotic fluid dopamine is related to initiation or maitenance of human parturition. In the present study, we demonstrated the presence of dopamine DA-1 receptor using [^3H]SCH23390, a dopamine DA-1 receptor ligand. The equilibrium dissociation constant (Kd) was 1.87 nM, and the maximum binding capacity (Bmax) was 79.0 fmol/mg protein. The competitive experiments using agents known to interact with DA-1 receptors and agents known to interact with DA-2 receptors and beta-adrenergic receptors dmonstrated that high-affinity binding sites for [^3H]SCH23390 was DA-1 receptor. Phosholipase A_2 (PLA_2) is considered to be the rate-limiting step in PG production. Recently, several isoforms of PLA_2 have been detected. Cytosolic 85 kD isoforms, named cytosolic PLA_2 (cPLA_2) is considered to release arachidonic acid for synthesis of PG via receptor stimulation. In the present study, PLA_2 in cytosol fraction of human amnion and decidua was characterized sn-2 fatty acid specificity and gel-filtration chromatography. The ratio of arachidonic acid to oleic acid release was 2.12 in amnion and 2.06 in decidua. The gel-filtration chromatography demonstrated that the molecular mass was about 85 kD.These results indicated this enzyme corresponds to the cPLA_2, The changes of cPLA_2 activity in amnion and decidua was studied during labor. At vaginal delivery, the activity in decidua was significantly lower than before the onset of labor. From these results, we suggest that the prostaglandin production in human decidua via dopamine receptors may be involved in initiation of labor.