Changes in expression of P2X7 receptors in rat myometrium at different gestational stages and the mechanism of ATP-induced uterine contraction

Given the importance of ATP in the control of uterine activity for successful labor and involution, this study was performed to measure the level of P2X7 receptors (P2X7Rs) in rat myometrium at different gestational stages and to investigate the mechanisms of ATP-induced uterine contraction. Myometrial tissues were obtained from rats at different gestational stages and the level of P2X7Rs was measured by ELISA. In other experiments, the effect of 1 mM ATP was tested on spontaneous contraction and the underlying mechanisms were investigated. P2X7Rs were expressed in nonpregnant uterine tissues, progressively increased throughout pregnancy, and markedly peaked during postpartum involution. ATP significantly increased the force of spontaneous contraction in all uterine strips from different gestational stages with marked increase during labor and postpartum. ATP could not maintain the force when external Ca2+ was removed. In addition, ATP was able to cause tonic transient contraction in the absence of external Ca2+. P2X7Rs are functionally regulated and contributed to ATP-induced uterine contraction. The sensitivity of the myometrium to ATP increases as pregnancy progresses and it involves Ca2+ influx and Ca2+ release pathways. The clear effects of ATP on contractility suggest its physiological requirement for successful labor and postpartum involution.