Oxytocin-induced phasic and tonic contractions are modulated by the contractile machinery rather than the quantity of oxytocin receptor

Dec 7, 2006American journal of physiology. Endocrinology and metabolism

Oxytocin causes short and long muscle contractions controlled by the contraction system, not by oxytocin receptor amount

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Abstract

The mRNA expression of the oxytocin receptor was greater at 19.0 days of gestation compared to nonpregnant phases.

Oxytocin-induced contractions were infrequent during the diestrus phase.
Low concentrations of oxytocin triggered all-or-none phasic contractions, which were inhibited by verapamil.
Tonic contractions at 19.0 days of gestation were significantly stronger than those during estrus.
In 19.0 days of gestation, large tonic contractions occurred even in PGF(2alpha) receptor knockout mice with low oxytocin receptor levels.
Tonic contractions in 19.0 days of gestation were influenced by both calcium influx through L-type calcium channels and store-operated calcium channels.
The Rho signaling pathway enhanced the force of tonic contractions by increasing calcium sensitivity.

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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(2+) channel alpha(1C)-subunit (alpha(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 alpha(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 pD(2) 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 PGF(2alpha) 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 alpha(1C). The tonic contractions in 19.0 G are dependent on both Ca(2+) influxes via L-type Ca(2+) channels and store-operated Ca(2+) channels, and the force is augmented by the Rho signal pathway, which increases the Ca(2+) sensitivity. Thus the uterine contractions are mainly controlled by the modification of contractile signal machinery rather than simply by the OTR quantity.

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Oxytocin-induced phasic and tonic contractions are modulated by the contractile machinery rather than the quantity of oxytocin receptor

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