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犬回结肠交界处S-亚硝基硫醇、一氧化氮和含氮能神经递质的药理学特性比较。

Comparison of the pharmacological profile of S-nitrosothiols, nitric oxide and the nitrergic neurotransmitter in the canine ileocolonic junction.

作者信息

De Man J G, Boeckxstaens G E, De Winter B Y, Moreels T G, Misset M E, Herman A G, Pelckmans P A

机构信息

Division of Gastroenterology, Faculty of Medicine, University of Antwerp (UIA), Antwerpen-Wilrijk, Belgium.

出版信息

Br J Pharmacol. 1995 Mar;114(6):1179-84. doi: 10.1111/j.1476-5381.1995.tb13331.x.

DOI:10.1111/j.1476-5381.1995.tb13331.x
PMID:7620707
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1510352/
Abstract
  1. In organ bath experiments, hydroquinone (30-100 microM) and hydroxocobalamin (30-100 microM) concentration-dependently inhibited the relaxations induced by NO (0.3-30 microM) but not those by nitroglycerin (GTN, 1 microM) in the canine ileocolonic junction (ICJ). Hydroxocobalamin reduced the relaxation to low frequency (2 Hz) stimulation of the non-adrenergic, non-cholinergic (NANC) nerves, whereas hydroquinone only reduced the NANC nerve-mediated relaxations to electrical stimulation at 16 Hz, 0.5 ms. 2. Relaxations to S-nitroso-L-cysteine (CysNO, 1-30 microM), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-30 microM) were not inhibited by hydroquinone (30-100 microM), hydroxocobalamin (30-100 microM), pyrogallol (30-100 microM) or L-cysteine (1-3 microM). Hydroquinone (100 microM) only reduced the relaxation to 10 microM CysNO. Hydroxocobalamin, but not hydroquinone, pyrogallol or L-cysteine, potentiated the relaxations to the lowest concentration (1 microM) of S-nitrosoglutathione (GSNO, 1-30 microM). 3. In the superfusion bioassay, hydroquinone (100 microM) and hydroxocobalamin (1 microM) concentration-dependently inhibited the biological activity of authentic NO (1-4 pmol) to the same extent as that of the transferable nitrergic factor, released from the canine ICJ in response to NANC nerve stimulation (8-16 Hz, 2 ms). Responses to GTN (10 pmol) or adenosine 5'-triphosphate (10 nmol) were not affected. 4. In conclusion, the nitrosothiols CysNO, SNAP and GSNO relax the canine ileocolonic junction, but these relaxations, pharmacologically, behave differently from the NANC nerve-mediated relaxations. From the bioassay experiments, we conclude that the nitrergic factor, released in response to NANCnerve stimulation of the canine ICJ, behaves pharmacologically like NO but not like a nitrosothiol.Therefore, we suggest NO, and not CysNO, SNAP or GSNO as the inhibitory NANC neurotransmitter in the canine ICJ.
摘要
  1. 在器官浴实验中,对犬回结肠交界处(ICJ)进行研究,对苯二酚(30 - 100微摩尔)和羟钴胺素(30 - 100微摩尔)呈浓度依赖性地抑制由一氧化氮(0.3 - 30微摩尔)诱导的舒张,但不抑制由硝酸甘油(GTN,1微摩尔)诱导的舒张。羟钴胺素降低了对非肾上腺素能、非胆碱能(NANC)神经低频(2赫兹)刺激的舒张反应,而对苯二酚仅降低了NANC神经介导的对16赫兹、0.5毫秒电刺激的舒张反应。2. 对亚硝基 - L - 半胱氨酸(CysNO,1 - 30微摩尔)或亚硝基 - N - 乙酰 - D,L - 青霉胺(SNAP,1 - 30微摩尔)的舒张反应不受对苯二酚(30 - 100微摩尔)、羟钴胺素(30 - 100微摩尔)、邻苯三酚(30 - 100微摩尔)或L - 半胱氨酸(1 - 3微摩尔)的抑制。对苯二酚(100微摩尔)仅降低了对10微摩尔CysNO的舒张反应。羟钴胺素而非对苯二酚、邻苯三酚或L - 半胱氨酸增强了对最低浓度(1微摩尔)亚硝基谷胱甘肽(GSNO,1 - 30微摩尔)的舒张反应。3. 在灌注生物测定中,对苯二酚(100微摩尔)和羟钴胺素(1微摩尔)呈浓度依赖性地抑制真实一氧化氮(1 - 4皮摩尔)的生物活性,其抑制程度与犬ICJ对NANC神经刺激(8 - 16赫兹,2毫秒)释放的可转移硝化因子相同。对GTN(10皮摩尔)或腺苷5'-三磷酸(10纳摩尔)的反应未受影响。4. 总之,亚硝基硫醇CysNO、SNAP和GSNO可使犬回结肠交界处舒张,但这些舒张反应在药理学上与NANC神经介导的舒张反应不同。从生物测定实验中,我们得出结论,犬ICJ对NANC神经刺激释放的硝化因子在药理学上表现得像一氧化氮而不像亚硝基硫醇。因此,我们认为在犬ICJ中抑制性NANC神经递质是一氧化氮,而非CysNO、SNAP或GSNO。

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本文引用的文献

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Differential effects of hydroxocobalamin on NO-mediated relaxations in rat aorta and anococcygeus muscle.羟钴胺对大鼠主动脉和肛门尾骨肌中一氧化氮介导的舒张作用的差异影响。
Br J Pharmacol. 1993 Jan;108(1):3-5. doi: 10.1111/j.1476-5381.1993.tb13429.x.
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S-nitrosocysteine, but not sodium nitroprusside, produces apamin-sensitive hyperpolarization in rat gastric fundus.S-亚硝基半胱氨酸而非硝普钠可使大鼠胃底产生蜂毒明肽敏感的超极化。
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Differential effects of hydroxocobalamin on relaxations induced by nitrosothiols in rat aorta and anococcygeus muscle.羟钴胺对大鼠主动脉和肛尾肌中硫代亚硝基化合物诱导的舒张作用的差异效应。
Eur J Pharmacol. 1993 Sep 14;241(2-3):249-54. doi: 10.1016/0014-2999(93)90210-9.
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Understanding the controversy over the identity of EDRF.了解关于内皮舒张因子(EDRF)身份的争议。
Nature. 1994 Mar 3;368(6466):62-5. doi: 10.1038/368062a0.
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