Endothelin-3 stimulates production of endothelium-derived nitric oxide via phosphoinositide breakdown

• Published in: Biochemical and biophysical research communications Vol. 174; no. 1; pp. 228 - 235
• Main Authors: Emori, Toshiaki, Hirata, Yukio, Kanno, Kazuo, Ohta, Kazuki, Eguchi, Satoru, Imai, Taihei, Shichiri, Masayoshi, Marumo, Fumiaki
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.01.1991; Elsevier
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cattle; Cell physiology; Cells, Cultured; Cyclic GMP - metabolism; Dose-Response Relationship, Drug; endothelin-3; Endothelins - administration & dosage; Endothelins - pharmacology; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - metabolism; Hormonal regulation; Inositol 1,4,5-Trisphosphate - metabolism; Molecular and cellular biology; nitric oxide; Nitric Oxide - metabolism; Pertussis Toxin; Phosphatidylinositols - metabolism; phosphoinositides; Virulence Factors, Bordetella - pharmacology; NO; EDRF; SNP; PTX; IP 3; [Ca 2+] i; VSMC; EC; l-NMMA; ET; Cell culture; Endothelial cell; Endothelin; Bovine; Peptide hormone; Islet activating protein; Dose activity relation; Vertebrata; Mammalia; Fluorescent labelling; Nitrogen monoxide; Vasoconstrictor agent; Artiodactyla; Endothelium derived relaxing factor; Ungulata; G protein
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(91)90510-E

Cultured bovine endothelial cells (EC) have specific receptors for endothelin (ET)-3 functionally coupled to phosphoinositide breakdown. We studied whether ET-3 stimulates synthesis of nitric oxide (NO), an endothelium-derived relaxing factor that activates soluble guanylate cyclase in EC, and whether the ET-3-induced NO formation involves G-proteins. ET-3 dose-dependently stimulated production of intracellular cGMP in EC, of which effects were abolished by pretreatment with N G-monomethyl l-arginine, an inhibitor of NO synthesis, and methylene blue, an inhibitor of soluble guanylate cyclase. The stimulatory effects of ET-3 on cGMP production, inositol trisphosphate formation and increase in cytosolic free Ca 2+ concentration were similarly blocked by pretreatment with pertussis toxin (PTX). These data suggest that ET-3 induces synthesis of NO mediated by phosphoinositide breakdown via PTX-sensitive G-protein in EC.