Effect of endothelin-1(1-31) on intracellular free calcium in cultured human mesangial cells

We found that human chymase selectively produces 31-amino-acid length endot helins (1-31) (ETs(1-31)). We investigated the effect of synthetic ET-l(1-3 1) on intracellular free Ca2+ concentration ([Ca2+](i)) in cultured human m esangial cells. ET-l(1-31) increased [Ca2+](i) in a concentration-dependent manner to a similar extent as ET-1. The ET-1 (1-31)-induced [Ca2+](i) incr ease was not influenced by removal of extracellular Ca2+ but was inhibited by thapsigargin. ET-l(1-31)-induced [Ca2+](i) increase was not affected by phosphoramidon. It was inhibited by BQ123, but not by BQ788. These results suggest that ET-l(1-31) by itself exhibits bioactive properties probably th rough endothelin ETA or ETA-like receptors. Since human chymase has been re ported to exist in the kidney, ET-l(1-31) may be a candidate substance for mesangium-relevant diseases. (C) 1999 Elsevier Science Inc.