Nitric oxide- and hydrogen peroxide-mediated gene expression by glucocorticoids and FK506 in histamine paw edema of mice.
An immunosuppressant FK506 binds with a component (hsp 56) of glucocorticoid receptor (GR) complex. Dexamethasone (Dex) never suppressed histamine paw edema of mice before 1 hr after its dosing as new protein(s) synthesis is required. However, FK506 (0.01-10 mg/kg, oral) 1.5 hr before 0.1 mg/kg Dex (s.c.), suppressed edema at 30 min. This suppression and that at 3 hr, were abolished by nitric oxide (NO) synthesis inhibitors (1-300 mg/kg). Nitroprusside (NO donor), catalase and molybdate (GR complex stabilizing protease inhibitor) enhanced the suppression. FK506, not cyclosporin A, was demonstrated for the first time in vivo to enhance GR and a hypothesis is proposed that FK506 might enhance GR and AP-1 signalings in a system reciprocally controlled by NO and H2O2.
Oyanagui
Y
Y
2nd Pharmacology, Drug Develop. Lab. of Fujisawa Pharmaceut. Co., Osaka, Japan.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006632:Histamine; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology*; D014178:Translocation, Genetic
D017382:Reactive Oxygen Species; D011965:Receptors, Glucocorticoid; D009569:Nitric Oxide; D003907:Dexamethasone; D006632:Histamine; D001120:Arginine; D006861:Hydrogen Peroxide; D002374:Catalase; D019331:NG-Nitroarginine Methyl Ester; D016559:Tacrolimus