EFFECT OF ENDOTHELIN-1(1-31) ON INTRACELLULAR FREE CALCIUM IN CULTURED HUMAN MESANGIAL CELLS

Abstract We found that human chymase selectively produces 31-amino-acid length endothelins (1–31) (ETs(1–31)). We investigated the effect of synthetic ET-1(1–31) on intracellular free Ca 2+ concentration ([Ca 2+ ] i ) in cultured human mesangial cells. ET-1(1–31) increased [Ca 2+ ] i in a concentration-dependent manner to a similar extent as ET-1. The ET-1 (1–31)-induced [Ca 2+ ] i increase was not influenced by removal of extracellular Ca 2+ but was inhibited by thapsigargin. ET-l(l–31)-induced [Ca 2+ ] i increase was not affected by phosphoramidon. It was inhibited by BQ123, but not by BQ788. These results suggest that ET-1(1–31) by itself exhibits bioactive properties probably through endothelin ET A or ET A -like receptors. Since human chymase has been reported to exist in the kidney, ET-1(1–31) may be a candidate substance for mesangiumrelevant diseases.