Lysophosphatidic acid (LPA) is known to increase uterine contraction in the estrus cycle and early pregnancy, however, the effect of LPA in late pregnant uterus and its mechanisms are not clear. In the present study, we show the LPA receptor subtypes expressed and the mechanism of LPA-induced contractions in late pregnant mouse uterus. We determined the relative mRNA expression of LPA receptor genes by quantitative PCR and elicited log concentration-response curves to oleoyl-L-α-LPA by performing tension experiments in the presence and absence of nonselective and selective receptor antagonists and inhibitors of the TXA2 pathway. LPA1 was the most highly expressed receptor subtype in the late pregnant mouse uterus and LPA1/2/3 agonist (Oleoyl-L-α LPA) elicited increased contractions in this tissue that had lesser efficacy compared to oxytocin. LPA1/3 antagonist, Ki-16425, and a potent LPA1 antagonist (AM-095) significantly inhibited the LPA-induced contractions. Further, the nonselective COX inhibitor, indomethacin, and potent thromboxane A2 synthase inhibitor, furegrelate significantly impaired LPA-induced contractions. Moreover, selective thromboxane receptor (TP) antagonist, SQ-29548, and Rho kinase inhibitor, Y-27632 almost eliminated LPA-induced uterine contractions. LPA1 stimulation elicits contractions in the late pregnant mouse uterus using the contractile prostanoid, TXA2 and may be targeted to induce labor in uterine dysfunctions/ dystocia.

已知溶血磷脂酸（LPA）在发情周期和早孕期增加子宫收缩，然而，LPA对晚孕子宫的影响及其机制尚不清楚。在本研究中，我们展示了 LPA 受体亚型的表达以及 LPA 诱导晚期妊娠小鼠子宫收缩的机制。我们通过定量 PCR 确定了 LPA 受体基因的相对 mRNA 表达，并通过在存在和不存在非选择性和选择性受体拮抗剂的情况下进行张力实验，得出对油酰-L-α-LPA 的对数浓度-反应曲线和 TXA2 途径的抑制剂。LPA1 是晚期妊娠小鼠子宫中表达最高的受体亚型，LPA1/2/3 激动剂（油酰-L-α LPA）引起该组织收缩增加，与催产素相比效果较差。LPA1/3 拮抗剂、Ki-16425 和强效 LPA1 拮抗剂 (AM-095) 显着抑制 LPA 诱导的收缩。此外，非选择性 COX 抑制剂、吲哚美辛和强效血栓素 A2合酶抑制剂 furegrelate 显着损害了 LPA 诱导的收缩。此外，选择性血栓烷受体 (TP) 拮抗剂 SQ-29548 和 Rho 激酶抑制剂 Y-27632 几乎消除了 LPA 诱导的子宫收缩。LPA1 刺激使用收缩剂引起晚期妊娠小鼠子宫收缩前列腺素、TXA2，并可能用于在子宫功能障碍/难产中诱导分娩。