Role of nitric oxide in histamine release from human basophils and rat peritoneal mast cells

The effects of a range of nitric oxide (NO)-related compounds on histamine release from human basophils and rat peritoneal mast cells were studied. Ba sal and immunologic histamine releases from human basophils were not affect ed by N-omega-nitro-L-arginine, N-omega-nitro-L-arginine methyl ester, amin oguanidine or methylene blue (all inhibitors of NO production), sodium nitr oprusside (an NO donor), L-arginine (a substrate for NO synthase) or D-argi nine (the inactive enantiomer of L-arginine). In rat peritoneal mast cells, NO donors such as sodium nitroprusside, sodium nitrite and sodium nitrate, and lipopolysaccharide (an inducer of NO synthase) had little effect on ba sal histamine release, while 3-morpholino-sydnonimine (SIN-1, an NO donor), L-arginine and D-arginine increased this release by up to threefold. None of the inhibitors of NO production had any striking effect on histamine rel ease induced by anti-rat immunoglobulin E (IgE), compound 48/80, sodium flu oride, phospholipase C, 1,2-dioctanoyl-sn-glycerol or ionophore A23187. How ever, haemoglobin was found to inhibit histamine release by anti-rat IgE or A23187 by ca. 40%. Alone of the NO donors, low concentrations Of L-arginin e produced a mild inhibition of histamine release induced by anti-IgE, comp ound 48/80 and A23187, but not other ligands, while sodium nitroprusside do se-dependently inhibited (by a maximum of ca. 30%) histamine release by ant i-rat IgE, sodium fluoride or A23187. Stimulation with a variety of secreta gogues or treatment with L-arginine, D-arginine, lipopolysaccharide, SIN-1 or sodium nitroprusside had no effect on NO production. Similarly, L-argini ne, D-arginine or sodium nitroprusside did not change intracellular cGMP le vels. On the basis of these results, it is suggested that NO does not play a significant role in the modulation of histamine release from human basoph ils or rat peritoneal mast cells. The effects Of L-arginine, D-arginine and sodium nitroprusside may involve mechanisms unrelated to NO. (C) 2001 Else vier Science B.V. All rights reserved.