title: Increase of L-type Ca2+ current by protease-activated receptor 2 activation contributes to augmentation of spontaneous uterine contractility in pregnant rats.
abstract: We evaluated the effects of protease-activated receptor (PAR)-2 on spontaneous myometrial contraction (SMC) in isolated term pregnant myometrial strips of rat, and elucidated the cellular mechanisms of this effect using a conventional voltage-clamp method. In isometric tension measurements, trypsin and SL-NH(2), PAR-2 agonists, significantly augmented SMC in frequency and amplitude; however, boiled trypsin (BT) and LR-NH(2) had no effect on SMC. These stimulatory effects of PAR-2 agonists on SMC were nearly completely occluded by pre-application of Bay K 8644, an L-type voltage-gated Ca(2+) channel activator, thus showing the involvement of L-type voltage-gated Ca(2+) channels in PAR-2-induced augmentation of SMC. In addition, PAR-2 agonists significantly enhanced L-type voltage-gated Ca(2+) currents (I(Ca-L)), as measured by a conventional voltage-clamp method, and this increase was primarily mediated by activation of phospholipase C (PLC) and protein kinase C (PKC) via G-protein activation. Taken together, we have demonstrated that PAR-2 may actively regulate SMC during pregnancy by modulating Ca(2+) influx through L-type voltage-gated Ca(2+) channels, and that this increase of I(Ca-L) may be primarily mediated by PLC and PKC activation. These results suggest a cellular mechanism for the pathophysiological effects of PAR-2 activation on myometrial contractility during pregnancy and provide basic and theoretical information about developing new agents for the treatment of premature labor and other obstetric complications.
authors.affiliation: Brain Korea 21 Project for Medical Science, Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Kim
authors.forename: Seungsoo
authors.initials: S
authors.lastname: Chung
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Eok-Cheon
authors.initials: EC
authors.lastname: Kim
authors.forename: Duck-Sun
authors.initials: DS
authors.lastname: Ahn
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D014590:Uterine Contraction; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D044464:Receptor, PAR-2; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011493:Protein Kinase C; D010738:Type C Phospholipases