一氧化氮供体对大鼠胃肌间神经丛一氧化氮合成的抑制作用。

Inhibitory effects of nitric oxide donors on nitric oxide synthesis in rat gastric myenteric plexus.

作者信息

Hosoda K, Takahashi T, Fujino M A, Owyang C

机构信息

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.

出版信息

J Pharmacol Exp Ther. 1998 Sep;286(3):1222-30.

PMID:9732382

Abstract

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.

摘要

我们研究了一氧化氮（NO）是否对大鼠胃肌间神经丛自身的合成产生抑制作用。对跨壁电刺激（TS）产生的非肾上腺素能、非胆碱能舒张反应，被NG-硝基-L-精氨酸甲酯（10⁻⁴M）显著拮抗，并被河豚毒素（10⁻⁶M）消除。用各种NO供体（3-吗啉代-西多奈德[SIN-1（3×10⁻⁷至3×10⁻⁶M）]、S-亚硝基-N-乙酰青霉胺（10⁻⁶至10⁻⁵M）、硝普钠（10⁻⁸至3×10⁻⁸M）和8-溴鸟苷3',5'-环一磷酸[8-溴-cGMP（10⁻⁶至3×10⁻⁶M）]）预处理，以剂量依赖的方式显著抑制了TS诱发的非肾上腺素能、非胆碱能舒张。相反，血管活性肠肽（10⁻⁸M）诱导的舒张不受SIN-1或8-溴-cGMP的影响。TS引起3H-瓜氨酸生成显著增加，这被无钙培养基、NG-硝基-L-精氨酸甲酯（10⁻⁴M）和河豚毒素（10⁻⁶M）完全消除。TS诱发的3H-瓜氨酸生成被SIN-1（10⁻⁷至10⁻⁵M）和8-溴-cGMP（10⁻⁷至10⁻⁵M）以剂量依赖的方式显著抑制。SIN-1的抑制作用被鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[3,4-a]喹喔啉-1-酮（10⁻⁵M）部分阻断。我们得出结论，胃肌间神经丛中的NO合成受到NO和cGMP负调控。这提示了胃肌间神经丛中NO合成的一种自动调节反馈机制。