title: Role of superoxide dismutase enzymes and ascorbate in protection of nitrergic relaxation against superoxide anions in mouse duodenum.
abstract: OBJECTIVE
  The aim of this study was to investigate whether superoxide dismutase (SOD) enzymes and ascorbate play a role in the protection of the nitrergic relaxation against superoxide anion inhibition in the mouse duodenum.
  
  
  METHODS
  The effects of exogenous SOD, N,No-bis(salicylidene) ethylenediamine chloride (EUK-8; a synthetic cell-permeable mimetic of the manganese SOD [Mn-SOD] and ascorbate on relaxant responses induced by nitrergic nerve stimulation), exogenous nitric oxide (NO), and nitroglycerin were investigated in isolated mouse duodenum tissues.
  
  
  RESULTS
  Diethyldithiocarbamate (DETCA) inhibited the relaxation to exogenous NO and nitroglycerin, but not relaxation to electrical field stimulation (EFS). SOD and ascorbate partially prevented the inhibitory effect of DETCA on relaxation to NO, abut not to nitroglycerin. The DETCA-induced inhibition on nitroglycerin was prevented by EUK-8. Hemoglobin, 2- (4-carboxyphenyl)-4,4,5,5-tetramethylimidazolinel-oxyl-3-oxide, and hydroxocobalamin inhibited the relaxation to NO, but not to EFS and nitroglycerin in the presence of DETCA. Pyrogallol and hydroquinone inhibited the relaxation to NO, but not to EFS and nitroglycerin. This inhibition was prevented by exogenous SOD and ascorbate, but was not prevented by EUK-8. Pyrogallol and hydroquinone did not inhibit the EFS-induced relaxation in the presence of DETCA. Duroquinone and 6-anilino-5.8-quinolinedione inhibited the relaxation to EFS, NO, and nitroglycerin, and this inhibition was prevented by EUK-8.
  
  
  CONCLUSIONS
  These results suggest that the nitrergic neurotransmission in the mouse duodenum is protected by endogenous tissue antioxidants against superoxide anions, and Mn SOD, in addition to copper/zinc SOD, can protect NO from attack from superoxide anion generators intracellularly. Also, the possibility that the endogenous neurotransmitter may not be the free NO but a NO-containing or NO-generating molecule in the mouse duodenum remains open.
authors.affiliation: Department of Pharmacology, Cukurova University, Adana 01330, Turkey.
authors.forename: M Ata
authors.initials: MA
authors.lastname: Secilmis
authors.forename: Olcay Ergurhan
authors.initials: OE
authors.lastname: Kiroğlu
authors.forename: Nuran
authors.initials: N
authors.lastname: Ogulener
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009942:Organometallic Compounds / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D005029:Ethylenediamines; D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D016877:Oxidants; D013481:Superoxides; D009569:Nitric Oxide; D004958:Estradiol; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); C073106:3,17-diacetoxyestra-1,3,5(10)-trien-2-carboxylic acid; D013482:Superoxide Dismutase; D001205:Ascorbic Acid