TXA2 mediates LPA1-stimulated uterine contraction in late pregnant mouse

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.

 

Comments：

The present study investigated the effect of Lysophosphatidic acid (LPA) on uterine contractions in late pregnant mice and its mechanisms. The researchers used quantitative PCR to determine the relative mRNA expression of LPA receptor genes and performed tension experiments to elicit log concentration-response curves to oleoyl-L-α-LPA. The results showed that LPA1 was the most highly expressed receptor subtype in the late pregnant mouse uterus, and LPA1/2/3 agonist elicited increased contractions in this tissue with lesser efficacy compared to oxytocin.

To further investigate the mechanism of LPA-induced contractions, the researchers used nonselective and selective receptor antagonists and inhibitors of the TXA2 pathway. The LPA1/3 antagonist, Ki-16425, and the potent LPA1 antagonist (AM-095) significantly inhibited LPA-induced contractions. The nonselective COX inhibitor, indomethacin, and potent thromboxane A2 synthase inhibitor, furegrelate, also impaired LPA-induced contractions. Moreover, the selective thromboxane receptor (TP) antagonist, SQ-29548, and Rho kinase inhibitor, Y-27632, almost eliminated LPA-induced uterine contractions.

Overall, the study suggests that LPA1 stimulation elicits contractions in the late pregnant mouse uterus using the contractile prostanoid, TXA2. The findings may have implications for inducing labor in uterine dysfunctions or dystocia.

Related Products

Cat.No.	Product Name	Information
S6633	AM 095	AM095 is an antagonist of the LPA type 1 receptor with IC50 values of 0.98 and 0.73 μM for recombinant human and mouse LPA1, respectively.

Related Targets

LPA Receptor