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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
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
10.1016/j.bbrc.2011.12.154
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
김억천(Kim, Eok Cheon)
김영환(Kim, Young Hwan)
안덕선(Ahn, Duk Sun) ORCID logo https://orcid.org/0000-0001-9351-6951
이영호(Lee, Young Ho) ORCID logo https://orcid.org/0000-0002-5749-1045
정승수(Chung, Seung Soo) ORCID logo https://orcid.org/0000-0002-3119-9628
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89691
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