Diazepam decreases leukocyte-endothelium interactions in situ.
High doses of diazepam reduce the inflammatory paw edema in rats. This effect was attributed to an action of diazepam on the Translocator Protein (TSPO). We evaluated the effects of diazepam (10 mg/kg, intraperitoneally) on leukocyte rolling and migration. In carrageenan-induced acute inflammation, diazepam decreased the interaction of leukocytes with endothelial cells (rolling) and the number of leukocytes in the mesentery (migration). RU486 (antagonist of glucocorticoid receptors) reduced the effects of diazepam on leukocyte rolling and migration, suggesting a participation of endogenous corticosteroids. We also showed that the effects of diazepam on leukocyte-endothelium interactions are mediated by nitric oxide (NO), since prior treatment with l-arginine (precursor of NO) partially precludes the inhibitory effects of diazepam; conversely, pretreatment with L-NAME (false substrate of the NO synthase) somewhat potentiates the effects of diazepam. The pathways that underlie the effects of diazepam remain to be further elucidated, but we believe that both local and systemic mechanisms may overlap to explain the influence of diazepam on leukocyte-endothelium interactions.
Lazzarini
R
R
Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine and Animal Science, São Paulo University, São Paulo, Brazil.
Sakai
M
M
Costa-Pinto
F A
FA
Palermo-Neto
J
J
D000818:Animals; D001120:Arginine / Q000378:metabolism; D002351:Carrageenan / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D007249:Inflammation / Q000276:immunology*; D036904:Leukocyte Rolling / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008643:Mesentery / Q000187:drug effects / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D011619:Psychotropic Drugs; D009569:Nitric Oxide; D015735:Mifepristone; D002351:Carrageenan; D001120:Arginine; D019001:Nitric Oxide Synthase; D003975:Diazepam; D019331:NG-Nitroarginine Methyl Ester