Endothelin-1-(1-31), a novel vasoactive peptide, increases [Ca2+]i in human coronary artery smooth muscle cells

European Journal of Pharmacology
M YoshizumiT Tamaki

Abstract

We have previously found that human chymase cleaves big endothelins at the Tyr31-Gly32 bond and produces 31-amino acid long endothelins-(1-31), without any further degradation products. In this study, we investigated the effect of synthetic endothelin-1-(1-31) on the intracellular free Ca2+ concentration ([Ca2+]i) in cultured human coronary artery smooth muscle cells. Endothelin-1-(1-31) increased [Ca2+]i in a concentration-dependent manner (10(-14) to 10(-10) M). This endothelin-1-(1-31)-induced [Ca2+]i increase was not affected by phosphoramidon (N-(alpha-Rhamnopyranosyloxyhydroxyphosphinyl)-L-Leucyl-L-Tryptoph an), an inhibitor of endothelin-converting enzyme. It was, however, inhibited by 10(-10) M BQ123 (Cyclo-(-D-Trp-D-Asp(ONa)-Pro-D-Val-Leu-)), an endothelin ET(A) receptor antagonist, but not by 10(-10) M BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-yMeLeu-D-Trp(COOM e)-D-Nle-ONa), an endothelin ET(B) receptor antagonist. These results suggest that endothelin-1-(1-31) by itself exhibits vasoactive properties probably through endothelin ET(A) receptors. Since human chymase has been reported to play a role in atherosclerosis, endothelin-1-(1-31) may be one of the candidate substances for its cause.

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Citations

Mar 31, 2011·General Thoracic and Cardiovascular Surgery·Eiki FujimotoTetsuya Kitagawa
Jan 7, 2004·Life Sciences·Sae KakuiYutaka Nakaya
Aug 24, 1999·British Journal of Pharmacology·Y Hayasaki-KajiwaraM Nakajima
Jul 12, 2002·British Journal of Pharmacology·Jean-Claude HonoréPedro D'Orléans-Juste
Jun 17, 2004·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Chihiro TanakaToshiyuki Miyata
Jul 16, 2004·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Keisuke IshizawaToshiaki Tamaki
Aug 5, 2008·Vascular Pharmacology·P D'Orléans-JusteE Simard
May 21, 2004·British Journal of Clinical Pharmacology·Stephen J LeslieDavid J Webb
Oct 29, 2005·European Journal of Pharmacology·Takashi KonnoMizuo Miyazaki

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