Submitted on September 12, 2006
Accepted on November 28, 2006
Oxytocin-induced phasic and tonic contractions are modulated by the contractile machinery rather than the quantity of oxytocin receptor
Masaki Kawamata1, Yutaka Tonomura2, Tadashi Kimura3, Yukihiko Sugimoto4, Teruyuki Yanagisawa5, and Katsuhiko Nishimori1*
1 Molecular Biology, Tohoku University, Sendai, Japan
2 Department of Molecular Biology, Tohoku University, Sendai , Japan
3 Division of Obstetrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
4 Department of Physiological Chemistry, Graduate School of Pharmaceutical Science, Kyoto University, Japan
5 Department of Molecular Pharmacology, Tohoku University, 980-8575, Sendai, Japan
* To whom correspondence should be addressed. E-mail: knishimo{at}mail.tains.tohoku.ac.jp.
To investigate the relationship between the oxytocin (OT) receptors (OTR) quantity and the contractile features systematically, we measured the mRNA expression levels of OTR and L-type Ca2+ 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 non-pregnant 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 prostaglandin F2 receptor (FP) knockout mice in 19.0 G despite small amount of OTR. Verapamil and Y-27632 partially inhibited the tonic contractions in 19.0 G. CPA-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 large tonic contractions in 19.0 G are dependent on both Ca2+ influxes via L-type Ca2+ channels and store-operated Ca2+ channels, and the force is augmented by the Rho signal pathway which increases the Ca2+ sensitivity. Thus, the uterine contractions are mainly controlled by the modification of contractile signal machinery rather than simply by the OTR quantity.
