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. Endocrinology and Metabolism 276(6): E1067-E1072

2018


ISSN/ISBN: 0193-1849
PMID: 29597454
DOI: 10.1152/ajpendo.1999.276.6.e1067
Accession: 065304918

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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 (10-14-10-10M). This ET-1-(1-31)-induced [Ca2+]iincrease was not affected by phosphoramidon, Bowman-Birk inhibitor, and thiorphan. The ET-1-(1-31)-induced [Ca2+]iincrease 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+]iincrease 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.