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

Young Hwan Kim, Seungsoo Chung, Young Ho Lee, Eok Cheon Kim, Duck Sun Ahn

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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-NH2, PAR-2 agonists, significantly augmented SMC in frequency and amplitude; however, boiled trypsin (BT) and LR-NH2 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 Ca2+ channel activator, thus showing the involvement of L-type voltage-gated Ca2+ channels in PAR-2-induced augmentation of SMC. In addition, PAR-2 agonists significantly enhanced L-type voltage-gated Ca2+ currents (ICa-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 Ca2+ influx through L-type voltage-gated Ca2+ channels, and that this increase of ICa-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.

Original languageEnglish
Pages (from-to)167-172
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume418
Issue number1
DOIs
StatePublished - Feb 3 2012
Externally publishedYes

Keywords

  • L-type voltage-gated Ca channel
  • Preterm labor
  • Protease-activated receptor-2
  • Uterine contractility

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