RT Journal Article
SR Electronic
T1 Inhibitory Effects of Nitric Oxide Donors on Nitric Oxide Synthesis in Rat Gastric Myenteric Plexus
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1222
OP 1230
VO 286
IS 3
A1 Kenji Hosoda
A1 Toku Takahashi
A1 Masayuki A. Fujino
A1 Chung Owyang
YR 1998
UL http://jpet.aspetjournals.org/content/286/3/1222.abstract
AB We investigated whether nitric oxide (NO) exerts an inhibition on its own synthesis in the gastric myenteric plexus in rats. Nonadrenergic, noncholinergic relaxations in response to transmural electrical stimulation (TS) were markedly antagonized by NG-nitro-l-arginine methyl ester, (10−4 M) and abolished by tetrodotoxin (10−6M). Pretreatment with various NO donors {3-morpholino-sydnonymide [SIN-1 (3 × 10−7 to 3 × 10−6M)], S-nitroso-N-acetylpenicillamine (10−6 to 10−5 M), sodium nitroprusside (10−8 to 3 × 10−8 M) and 8-bromoquanosine 3′,5′-cyclic monophosphate [8-bromo-cGMP (10−6 to 3 × 10−6M)]} significantly inhibited TS-evoked nonadrenergic, noncholinergic relaxations in a dose-dependent manner. In contrast, vasoactive intestinal polypeptide (10−8 M)-induced relaxations were not affected by SIN-1 or 8-bromo-cGMP. TS evoked a significant increase in 3H-citrulline formation, which was completely abolished by calcium-free medium, NG-nitro-l-arginine methyl ester, (10−4 M) and tetrodotoxin (10−6M). 3H-citrulline formation evoked by TS was significantly inhibited by SIN-1 (10−7 to 10−5 M) and 8-bromo-cGMP (10−7 to 10−5 M) in a dose-dependent manner. The inhibitory effect of SIN-1 was partially prevented by 1H-[1,2,4]oxadiazolo[3,4-a]quinoxalin-1-one (10−5 M), a guanylate cyclase inhibitor. We conclude that NO synthesis in the gastric myenteric plexus is negatively regulated by NO and cGMP. This suggests an autoregulatory feedback mechanism of NO synthesis in the gastric myenteric plexus. The American Society for Pharmacology and Experimental Therapeutics