Endothelin ET(A) receptor antagonist reverses the inhibitory effect of platelet-derived growth factor on cytokine-induced nitric oxide production.
Cytokines and cytokine-induced nitric oxide (NO) play important roles in inflammatory glomerular diseases, and both platelet-derived growth factor and transforming growth factor-beta inhibit cytokine-induced NO production. In this study, we demonstrated that a selective endothelin ET(A) receptor antagonist, BQ-485 (Hexahydro-1H-azepinylcarbonyl-Leu-D-Trp-D-Trp-OH), reversed the inhibitory effect of platelet-derived growth factor on cytokine-induced NO production, but not that of transforming growth factor-beta. Our findings suggest a difference between the inhibitory mechanisms of platelet-derived growth factor and transforming growth factor-beta on cytokine-induced NO production.
Hirahashi
J
J
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Nakaki
T
T
Hishikawa
K
K
Marumo
T
T
Hayashi
M
M
Saruta
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D000077214:Becaplermin; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D065128:Endothelin Receptor Antagonists; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D016212:Transforming Growth Factor beta / Q000494:pharmacology