ENDOTHELIN-1-(1-31), A NOVEL VASOACTIVE PEPTIDE, INCREASES [CA2-ARTERY SMOOTH-MUSCLE CELLS(](I) IN HUMAN CORONARY)

We have previously found that human chymase cleaves big endothelins at the Tyr(31)-Gly(32) bond and produces 31-amino acid long endothelins- (1-31), without any further degradation products. In this study, we in vestigated the effect of synthetic endothelin-1-(1-31) on the intracel lular free Ca2+ concentration([Ca2+](i)) in cultured human coronary ar tery smooth muscle cells. Endothelin-1-(1-31) increased [Ca2+](i) in a concentration-dependent manner (10(-14) to 10(-10) M), This endotheli n-1-(1-31)-induced [Ca2+](i) increase was not affected by phosphoramid on nosyloxyhydroxyphosphinyl)-L-Leucyl-L-Tryptophan), an inhibitor of endothelin-converting en zyme. It was, however, inhibited by 10(-10) M BQ123 (Cyclo-(-D-Trp-D-Asp(ONa)-Pro-D-Val-Leu-)) endothelin ETA recep tor antagonist, but not by 10(-10) M BQ788 (N-cis-2,6-dimethylpiperidi nocarbonyl-L-gamma MeLeu-D-Trp(COOMe)-D-Nle-ONa), an endothelin ETB re ceptor antagonist. These results suggest that endothelin-1-(1-31) by i tself exhibits vasoactive properties probably through endothelin ETA r eceptors. Since human chymase has been reported to play a role in athe rosclerosis, endothelin-1-(1-31) may be one of the candidate substance s for its cause. (C) 1998 Elsevier Science B.V. All rights reserved.