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 endothelins (1-31) (ETs(1-31)). We investigated the effect of synthetic ET-1(1-31) on intracellular free Ca2+ concentration ([Ca2+]i) in cultured human mesangial cells. ET-1(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 increase was not influenced by removal of extracellular Ca2+ but was inhibited by thapsigargin. ET-1(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-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 mesangium-relevant diseases.
Yasuoka
H
H
Department of Pharmacology, The University of Tokushima School of Medicine, Japan.
Yoshizumi
M
M
Inui
D
D
Okishima
N
N
Houchi
H
H
Kirima
K
K
Oshita
S
S
Kido
H
H
Tamaki
T
T
D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D053818:Chymases; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology / Q000031:analogs & derivatives; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008666:Metalloendopeptidases; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; C114932:endothelin-1 (1-31); D019284:Thapsigargin; D012697:Serine Endopeptidases; D053818:Chymases; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium; C008890:phosphoramidon