Opposite effect of superoxide dismutase, L-arginine analogues, methylene blue and desferal: suppression of histamine-induced and stimulation of serotonin-induced paw edema in mice.
Endogenous nitric oxide (NO, endothelium-derived relaxing factor) was stimulatory for histamine- and suppressive for serotonin-induced paw edema of mice. This action was mediated by guanosine 3',5'-cyclic monophosphate production. Local injection of superoxide dismutase (SOD), catalase, NG-monomethyl-L-arginine (L-NMMA), methylene blue and Desferal (iron chelator) mixed with mediator suppressed histamine-induced edema at doses between 0.1 and 100 micrograms/kg and showed no or little stimulatory effect at higher doses. L-arginine reversed the effect of L-NMMA. Serotonin edema was enhanced by a high dose of these drugs. Their effect became suppressive as the histamine ratio was increased in edema induced by a histamine-serotonin mixture. This suggested that serotonin-induced vascular permeability decreased with a greater production of either O2- or NO. Cimetidine (H2-antagonist) was not effective in histamine edema of normal mice, but became suppressive (ED50 = 70 micrograms/kg) when 10 mg/kg L-NMMA was coinjected. SOD and methylene blue also rendered this edema sensitive to cimetidine. A simultaneous decrease in sensitivity to mepyramine (H1-antagonist) indicated that NO and oxyradicals kept H1-receptors activated. L-NMMA had no effect on bradykinin edema, but suppressed thrombin-, acetylcholine-, platelet-activating factor-, substance P- and FeCl3-induced paw edemata. Nitroprusside (NO donator) suppressed serotonin edema. N-Acetylcysteine and cytochrome c, but not ascorbate and hydroxyl radical scavengers suppressed histamine edema.
Oyanagui
Y
Y
Drug Development Laboratory, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
Sato
S
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D012701:Serotonin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D019323:omega-N-Methylarginine
D000975:Antioxidants; D019323:omega-N-Methylarginine; D012701:Serotonin; D006632:Histamine; D001120:Arginine; D013482:Superoxide Dismutase; D003676:Deferoxamine; D008751:Methylene Blue