title: Role of nitric oxide in histamine release from human basophils and rat peritoneal mast cells.
abstract: The effects of a range of nitric oxide (NO)-related compounds on histamine release from human basophils and rat peritoneal mast cells were studied. Basal and immunologic histamine releases from human basophils were not affected by N(omega)-nitro-L-arginine, N(omega)-nitro-L-arginine methyl ester, aminoguanidine or methylene blue (all inhibitors of NO production), sodium nitroprusside (an NO donor), L-arginine (a substrate for NO synthase) or D-arginine (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 basal 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 release induced by anti-rat immunoglobulin E (IgE), compound 48/80, sodium fluoride, phospholipase C, 1,2-dioctanoyl-sn-glycerol or ionophore A23187. However, 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-arginine produced a mild inhibition of histamine release induced by anti-IgE, compound 48/80 and A23187, but not other ligands, while sodium nitroprusside dose-dependently inhibited (by a maximum of ca. 30%) histamine release by anti-rat IgE, sodium fluoride or A23187. Stimulation with a variety of secretagogues or treatment with L-arginine, D-arginine, lipopolysaccharide, SIN-1 or sodium nitroprusside had no effect on NO production. Similarly, L-arginine, D-arginine or sodium nitroprusside did not change intracellular cGMP levels. 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 basophils or rat peritoneal mast cells. The effects of L-arginine, D-arginine and sodium nitroprusside may involve mechanisms unrelated to NO.
authors.affiliation: Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK.
authors.forename: K H
authors.initials: KH
authors.lastname: Peh
authors.forename: A
authors.initials: A
authors.lastname: Moulson
authors.forename: B Y
authors.initials: BY
authors.lastname: Wan
authors.forename: E K
authors.initials: EK
authors.lastname: Assem
authors.forename: F L
authors.initials: FL
authors.lastname: Pearce
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001491:Basophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008751:Methylene Blue / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012969:Sodium Fluoride / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D000906:Antibodies; D006146:Guanidines; D006454:Hemoglobins; D009566:Nitrates; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D007073:Immunoglobulin E; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; C002385:linsidomine; D006632:Histamine; C031618:sodium nitrate; D012969:Sodium Fluoride; D001120:Arginine; D008981:Molsidomine; D012977:Sodium Nitrite; C004479:pimagedine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester