title: Oxytocin-induced phasic and tonic contractions are modulated by the contractile machinery rather than the quantity of oxytocin receptor.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kawamata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tonomura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Yanagisawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nishimori
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000235:genetics; D002154:Calpain / Q000235:genetics; D004031:Diestrus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004971:Estrus; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010121:Oxytocin / Q000494:pharmacology / Q000502:physiology*; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000172:deficiency; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D054460:rho-Associated Kinases
chemical_list: D000577:Amides; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; C108830:Y 27632; D010121:Oxytocin; D014700:Verapamil; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D002154:Calpain; C000543:cyclopiazonic acid