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 (H(2)O(2)), 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 antigen (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 HR above the basal level. However, the NO-donors (sodium nitroprusside or NaNO(3)) 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 or 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 microM). H(2)O(2) (0.01-1.0 mM) on its own did not induce HR, but it had a potent inhibitory effect on DNP-HSA- or A23187-induced HR, which was not reversed by L-NA (1-100 microM). Taken together, it seems that neither the stimulatory 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 H(2)O(2) also does not involve NO and suggests a negative feedback regulatory role for the peroxide in the allergic inflammation.
Wan
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BY
Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK.
Peh
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Assem
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D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D000001:Calcimycin; D006632:Histamine; D012969:Sodium Fluoride; D006861:Hydrogen Peroxide; D008751:Methylene Blue