Effects of nitric oxide and hydrogen peroxide on histamine release from RBL-2H3 cells

We have studied the effect of nitric oxide (NO) and hydrogen peroxide (H2O2 ), two reactive oxygen species (ROS) on histamine release (HR) from RBL-2H3 cells, a rat mucosal-type mast cell line, Marked HR was elicited by antige n (DNP-HSA), calcium ionophore A23187, sodium fluoride or phospholipase C, but not with compound 48/80 or 1,2-dioctanoyl-sn-glycerol. The NO-synthase substrate L-arginine and its inactive enantiomer (D-arginine), each on its own, induced a small but significant increase in FIR above the basal level. However, the NO-donors (sodium nitroprusside or NaNO3) or the NO-synthase inducer lipopolysaccharide did not induce HR. Moreover, methylene blue (MB) , which inhibits guanylate cyclase and N-omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase, were also without effect on either the basal HR o r the L-arginine-induced HR. HR induced by A23187, DNP-HSA, sodium fluoride or phospholipase C was markedly reduced by MB, but mildly by L-NA (both at 1-100 muM). H2O2 (0.01-1.0 muM) on its own did not induce HR, but it had a potent inhibitory effect on DNP-HSA- or A23187-induced HR, which was not r eversed by L-NA (1-100 muM). Taken together, it seems that neither the stim ulatory nor the inhibitory effects of the NO-related compounds on HR can be attributed to NO, but rather to other mechanisms. The inhibition of HR by H2O2 also does not involve NO and suggests a negative feedback regulatory r ole for the peroxide in the allergic inflammation. (C) 2001 Elsevier Scienc e Inc. All rights reserved.