The influence of nitric oxide donors on the responses to nitrergic nerve stimulation in the mouse duodenum


Ogulener N. , Ergun Y., Dondas N., Dikmen A.

EUROPEAN JOURNAL OF PHARMACOLOGY, cilt.421, ss.121-131, 2001 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 421 Konu: 2
  • Basım Tarihi: 2001
  • Doi Numarası: 10.1016/s0014-2999(01)01024-x
  • Dergi Adı: EUROPEAN JOURNAL OF PHARMACOLOGY
  • Sayfa Sayıları: ss.121-131

Özet

We investigated whether exogenous nitric oxide (NO) donors have a prejunctional and/or postjunctional inhibitory effect on the nitrergic responses and whether this inhibitory effect was mediated by NO itself and in part, by cyclic GMP in mouse duodenal strips. N-omega-nitro-L-arginine inhibited relaxations induced by electrical field stimulation of nitrergic nerves, but not those with acidified NaNO2. Furthermore, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) inhibited both types of relaxations while 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) and N-ethylmaleimide were ineffective. NO donors, nitroglycerin and sodium nitroprusside, inhibited relaxations induced by nitrergic nerve stimulation, but not those with acidified NaNO2. Hemoglobin, exogenous Cu2+/Zn2+ superoxide dismutase, diethyldithiocarbamic acid and pyrogallol did not influence the relaxation with nitrergic nerve stimulation. However, hemoglobin, diethyldithiocarbamic acid, pyrogallol and diethyldithiocarbamic acid plus pyrogallol attenuated the inhibitory effect of NO donors on relaxation with nitrergic nerve stimulation, and exogenous superoxide dismutase potentiated this inhibitory effect. Moreover, nitrergic nerve-mediated relaxations were inhibited by 8-bromo-cyclic GMP, but not by 8-bromo-cyclic AMP. These results suggest that exogenous NO donors have a prejunctional inhibitory effect on the nerve-mediated nitrergic relaxation and that the inhibitory effects of nitroglycerin and sodium nitroprusside are NO-dependent, but not related to NO metabolites such as peroxynitrite or a nitrosothiol intermediate. However, a contribution of S-nitrosothiol formed intracellularly cannot be entirely ruled out. Also, this prejunctional inhibition is mediated, at least in part, by the cyclic GMP, but not the cyclic AMP, pathway. (C) 2001 Elsevier Science B.V. All rights reserved.