title: Pharmacological profile of nitrergic nerve-, nitric oxide-, nitrosoglutathione- and hydroxylamine-induced relaxations of the rat duodenum.
abstract: Activation of inhibitory nonadrenergic noncholinergic (NANC) nerves in the rat duodenum cause relaxations, which are reduced by nitric oxide synthase (NOS) inhibitors indicating that this response involves a nitrergic neurotransmission. The precise nature of the nitrergic neurotransmitter is still controversial since nitric oxide (NO) scavengers and superoxide generators, even in the presence of superoxide dismutase inhibitors, failed to inhibit nitrergic neurotransmission mediated relaxations. In order to understand the role of NOS in nitrergic neurotransmission and considering that N-OH-arginine (OH-L-Arg), L-citrulline, NO, S-nitrosoglutathione (GSNO) and hydroxylamine (NH2OH) can be formed in cells during the N(G)-oxidation of L-arginine catalyzed by NOS we explored whether any of these products could exhibit biological properties comparable to those of the nitrergic neurotransmitter. After establishing which of them was able to relax the rat duodenum, the pharmacological profile of such effect was determined employing oxyhemoglobin (OxyHb), pyrogallol (PYR), hydroquinone (HQ), hydroxocobalamin (HC) or carboxy-PTIO (C-PTIO) and compared with that of nerve mediated relaxations. NO, GSNO and NH2OH, but not OH-L-ARG and L-citrulline, caused concentration-dependent relaxations that were not affected by tetrodotoxin or L-NOARG. OxyHb almost abolished NO-induced relaxations but decreased only marginally the magnitude of nerve-, NH2OH- and SNG-induced relaxations. PYR, HQ and C-PTIO reduced significantly GSNO- and NO- induced relaxations but did not affect those induced by NH2OH or nerve activation. In contrast, HC abolished NO-induced relaxations while it did not affect those induced by GSNO, NH2OH and nerve activation. The catalase inhibitor 1,2,4 aminotriazole failed to affect nerve and NH2OH induced relaxations. These findings indicate that among the products that can be formed during NOS catalyzed L-arginine N(G)-oxidation, only NH2OH caused relaxations that exhibited a pharmacological profile similar to those induced by the nitrergic neurotransmitter. Furthermore, if NH2OH is the actual neurotransmitter it appears to be acting either directly or by a catalase independent release of NO.
authors.affiliation: Departamento de Farmacologia e, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil.
authors.forename: N A
authors.initials: NA
authors.lastname: Correia
authors.forename: R B
authors.initials: RB
authors.lastname: Oliveira
authors.forename: G
authors.initials: G
authors.lastname: Ballejo
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D004386:Duodenum / Q000187:drug effects* / Q000294:innervation; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019811:Hydroxylamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D009603:Nitroso Compounds; D013481:Superoxides; D019811:Hydroxylamine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D013482:Superoxide Dismutase; D005978:Glutathione