Mechanism of endothelin-1- (1-31) -induced calcium signaling in human coronary artery smooth muscle cells

Inui, D.; Yoshizumi, M.; Okishima, N.; Houchi, H.; Tsuchiya, K.; Kido, H.; Tamaki, T.

American Journal of Physiology 276(6): E1067-E1072

1999


ISSN/ISBN: 0002-9513
PMID: 10362619
Accession: 010966237

Download citation:  
Text
  |  
BibTeX
  |  
RIS

Article/Abstract emailed within 1 workday
Payments are secure & encrypted
Powered by Stripe
Powered by PayPal

Abstract
We have found that human chymase produces a 31-amino acid endothelin (ET-1-(1-31)) from the 38-amino acid precursor (Big ET-1). We examined the mechanism of synthetic ET-1-(1-31)-induced intracellular Ca2+ signaling in cultured human coronary artery smooth muscle cells. ET-1-(1-31) increased the intracellular free Ca2+ concentration ((Ca2+)i) in a concentration-dependent manner (10-14-10-10 M). This ET-1-(1-31)-induced (Ca2+)i increase was not affected by phosphoramidon, Bowman-Birk inhibitor, and thiorphan. The ET-1-(1-31)-induced (Ca2+)i increase was not influenced by removal of extracellular Ca2+ but was inhibited by thapsigargin. ET-1-(1-31) at 10-12 M did not cause Ca2+ influx, whereas 10-7 M ET-1-(1-31) evoked marked Ca2+ influx, which was inhibited by nifedipine. ET-1-(1-31) also increased inositol trisphosphate formation. These results suggest that the ET-1-(1-31)-induced (Ca2+)i increase at relatively low concentrations is attributable to the release of Ca2+ from inositol trisphosphate-sensitive intracellular stores, whereas Ca2+ influx into the cells evoked by high concentration of ET-1-(1-31) probably occurs through voltage-dependent Ca2+ channels. We concluded that the physiological activity of ET-1-(1-31) may be attributable to Ca2+ mobilization from intracellular stores rather than influx of Ca2+ from extracellular space.