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 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.
MeSH terms
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Aspartic Acid Endopeptidases / antagonists & inhibitors
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Aspartic Acid Endopeptidases / metabolism
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Calcium / antagonists & inhibitors
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Calcium / metabolism*
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Cells, Cultured
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Chymases
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Dose-Response Relationship, Drug
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Endothelin-1 / pharmacology
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Endothelin-Converting Enzymes
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Endothelins / pharmacology*
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Glomerular Mesangium / drug effects
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Glomerular Mesangium / enzymology
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Glomerular Mesangium / metabolism*
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Glycopeptides / pharmacology
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Humans
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Intracellular Fluid / drug effects
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Intracellular Fluid / metabolism*
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Metalloendopeptidases
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Microscopy, Confocal
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Peptide Fragments / pharmacology*
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Peptides, Cyclic / pharmacology
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Protease Inhibitors / pharmacology
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Serine Endopeptidases / metabolism
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Thapsigargin / pharmacology
Substances
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Endothelin-1
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Endothelins
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Glycopeptides
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Peptide Fragments
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Peptides, Cyclic
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Protease Inhibitors
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endothelin-1 (1-31)
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Thapsigargin
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Serine Endopeptidases
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Chymases
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Aspartic Acid Endopeptidases
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Metalloendopeptidases
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Endothelin-Converting Enzymes
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cyclo(Trp-Asp-Pro-Val-Leu)
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Calcium
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phosphoramidon