Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells.
It was reported that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs(1-31). In this study, we investigated the effect of ET-1(1-31) on p38 mitogen-activated protein kinase (p38-MAPK) activity in human mesangial cells (HMCs). By measuring the kinase activity, we demonstrated that ET-1 (1-31) activated the p38-MAPK dose-dependently (10(-9) M to 10(-7) M), which was inhibited by SB203580. The p38-MAPK activation induced by ET-1(1-31) peaked at 10 minutes. BQ123 almost abolished ET-1(1-31)-induced p38-MAPK activation, whereas BQ788 failed to inhibit it. These findings suggest that the stimulatory effect of ET-1(1-31) on p38-MAPK activation is mediated through ET(A) or ET(A)-like receptor. In conclusion, ET-1(1-31) induced increase in p38-MAPK activation in cultured HMCs.
Inui
D
D
Department of Pharmacology, The University of Tokushima School of Medicine, Japan.
Yoshizumi
M
M
Suzaki
Y
Y
Kirima
K
K
Tsuchiya
K
K
Houchi
H
H
Kagami
S
S
Tamaki
T
T
D015153:Blotting, Western; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D013268:Stimulation, Chemical
D007093:Imidazoles; D011725:Pyridines; C093642:SB 203580