Kawamata M, Tonomura Y, Kimura T, Sugimoto Y, Yanagisawa T, Nishimori K. Oxytocin-induced phasic and tonic contractions are modulated by the contractile machinery rather than the quantity of oxytocin receptor. Am J Physiol Endocrinol Metab 292: E992-E999, 2007. First published December 5, 2006; doi:10.1152/ajpendo.00492.2006.-To investigate the relationship between the oxytocin (OT) receptor (OTR) quantity and the contractile features systematically, we measured the mRNA expression levels of OTR and L-type Ca 2ϩ channel ␣1C-subunit (␣1C) and examined the regulatory mechanisms of OT-induced phasic or tonic contractions of the longitudinal smooth muscles in mouse uteri. The mRNA expression of OTR in 19.0 G (19.0 days of gestation) was greater than those in nonpregnant phases, and that of ␣1C in estrus and 19.0 G was higher than in diestrus. OT-induced contractions sparsely occurred in diestrus. The OT-induced all-or-none-type phasic contractions at low concentrations were abolished by verapamil in both estrus and 19.0 G. OT-induced tonic contractions had similar pD2 values in both estrus and 19.0 G. However, the magnitude in 19.0 G was much greater than that in estrus. The large tonic contractions also occurred in PGF2␣ receptor (FP) knockout mice in 19.0 G despite a small amount of OTR. Verapamil and Y-27632 partially inhibited the tonic contractions in 19.0 G. Cyclopiazonic acid-induced tonic contractions were reciprocally decreased with the increase in the OT-induced ones in 19.0 G. These results indicate that the phasic contractions are dependent on ␣1C. The tonic contractions in 19.0 G are dependent on both Ca 2ϩ influxes via L-type Ca 2ϩ channels and store-operated Ca 2ϩ channels, and the force is augmented by the Rho signal pathway, which increases the Ca 2ϩ sensitivity. Thus the uterine contractions are mainly controlled by the modification of contractile signal machinery rather than simply by the OTR quantity.oxytocin; uterus; contraction; receptor quantity; mouse OXYTOCIN (OT) is a well-known neurohypophysial hormone that stimulates uterine contractions to facilitate parturition (11). The near-term myometrium is extremely sensitive to OT, and the increased responsiveness to OT occurs in parallel with an increase in the number of uterine OT binding sites in rats (6, 42), humans (7), rabbits (28, 29), and cows (8). A corresponding increase in uterine OT receptor (OTR) mRNA in late pregnancy and at parturition has been reported in rats (23,26,38), humans (21), cows (13), and sheep (51, 55). In human uterus at term, the sensitivity to OT is 200-to 1,000-fold greater than that during the menstrual cycle (1). Thus, although there has not yet been conclusive evidence, it has been believed that the sensitivity to OT depends on the OTR quantity.OT induces phasic or tonic contractions in myometrium. Phasic contractions are essential for the successful progression of labor, whereas tonic contractions may contribute to prevent atonic bleeding after parturition. During the course of parturition, prolonged tonic cont...