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Increase of L-type Ca2+ current by protease-activated receptor 2 activation contributes to augmentation of spontaneous uterine contractility in pregnant rats

Authors
 Young-Hwan Kim  ;  Seungsoo Chung  ;  Young-Ho Lee  ;  Eok-Cheon Kim  ;  Duck-Sun Ahn 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.418(1) : 167-172, 2012 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2012
MeSH
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology ; Animals ; Calcium Channel Agonists/pharmacology ; Calcium Channels, L-Type/metabolism* ; Enzyme Activation ; Female ; Myometrium/drug effects ; Myometrium/metabolism ; Myometrium/physiology ; Pregnancy ; Protein Kinase C/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, PAR-2/agonists ; Receptor, PAR-2/metabolism* ; Type C Phospholipases/metabolism ; Uterine Contraction* ; Uterus/drug effects ; Uterus/metabolism ; Uterus/physiology*
Keywords
Preterm labor ; Uterine contractility ; Protease-activated receptor-2 ; L-type voltage-gated Ca2+ channel
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X12000071
DOI
22244874
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eok Cheon(김억천)
Kim, Young Hwan(김영환)
Ahn, Duk Sun(안덕선) ORCID logo https://orcid.org/0000-0001-9351-6951
Lee, Young Ho(이영호) ORCID logo https://orcid.org/0000-0002-5749-1045
Chung, Seung Soo(정승수) ORCID logo https://orcid.org/0000-0002-3119-9628
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89691
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