Inhibitory effects of nitric oxide donors on nitric oxide synthesis in rat gastric myenteric plexus.
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(-6) M). Pretreatment with various NO donors (3-morpholino-sydnonymide [SIN-1 (3 x 10(-7) to 3 x 10(-6) M)], S-nitroso-N-acetylpenicillamine (10(-6) to 10(-5) M), sodium nitroprusside (10(-8) to 3 x 10(-8) M) and 8-bromoquanosine 3', 5'-cyclic monophosphate [8-bromo-cGMP (10(-6) to 3 x 10(-6) M)]) 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(-6) M). 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.
Hosoda
K
K
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Takahashi
T
T
Fujino
M A
MA
Owyang
C
C
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002956:Citrulline / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009197:Myenteric Plexus / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000294:innervation; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D015220:Calcium Channels; D009599:Nitroprusside; D002956:Citrulline; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester