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灌注兔肺中生物源性单胺的命运。

The fate of biogenic monoamines in perfused rabbit lung.

作者信息

Gillis C N, Roth J A

出版信息

Br J Pharmacol. 1977 Apr;59(4):585-90. doi: 10.1111/j.1476-5381.1977.tb07725.x.

Abstract
  1. Inactivation of beta-phenylethylamine and several of its derivatives was studied in a preparation of rabbit lung perfused with Krebs physiological medium at 37 degrees C. Inactivation or removal of these compounds was calculated as the difference between the concentration of each amine in the perfusion medium and the effluent, collected separately from each lung. The extent of amine metabolic degradation was also measured, by column chromatography, in lung effluent. 2. With this technique the magnitude of amine removal as a function of concentration was determined and an apparent Km and Vmax of removal were calculated for each amine. 3. Percentage removal was highest with phenylethylamine (95%), and decreased, apparently in relation to increasing phenyl- and side chain-hydroxylation (and therefore likely increased hydrophilicity), and 5-hydroxytryptamine (64%), tyramine (53%), octopamine (35%), dopamine (32%) and noradrenaline (23%). 4. Inactivation of each amine could be accounted for by metabolic degradation to deaminated products, which appeared in lung effluent within 90 s of beginning amine perfusion. 5. When intrapulmonary metabolism of phenylethylamine was inhibited by simultaneous perfusion with semicarbazide (10 mM) and pargyline (10 micronM), the removal rate was unaltered, establishing that uptake of the amine from the vascular space is not dependent on metabolism at least for 4 min infusions.
摘要
  1. 在37摄氏度下,用 Krebs 生理介质灌注兔肺的制备物中,研究了β-苯乙胺及其几种衍生物的失活情况。这些化合物的失活或清除量通过灌注介质和从每个肺分别收集的流出液中每种胺的浓度差来计算。还通过柱色谱法测量了肺流出液中胺代谢降解的程度。2. 用这种技术确定了胺清除量随浓度的变化幅度,并计算了每种胺的表观 Km 和最大清除速度(Vmax)。3. 苯乙胺的清除率最高(95%),并随着苯环和侧链羟基化程度的增加(因此可能亲水性增加)而降低,5-羟色胺(64%)、酪胺(53%)、章鱼胺(35%)、多巴胺(32%)和去甲肾上腺素(23%)的清除率也依次降低。4. 每种胺的失活可归因于代谢降解为脱氨基产物,这些产物在胺灌注开始后90秒内出现在肺流出液中。5. 当同时用氨基脲(10 mM)和优降宁(10 μM)灌注抑制苯乙胺的肺内代谢时,清除率未改变,这表明至少在4分钟的灌注过程中,胺从血管空间的摄取不依赖于代谢。

相似文献

1
The fate of biogenic monoamines in perfused rabbit lung.灌注兔肺中生物源性单胺的命运。
Br J Pharmacol. 1977 Apr;59(4):585-90. doi: 10.1111/j.1476-5381.1977.tb07725.x.
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Uptake and metabolism of biogenic amines in the developing rabbit lung.发育中兔肺内生物胺的摄取与代谢
J Appl Physiol Respir Environ Exerc Physiol. 1981 Jan;50(1):118-22. doi: 10.1152/jappl.1981.50.1.118.
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Simulation of biogenic amine metabolism in the brain.大脑中生物胺代谢的模拟
Biochem J. 1974 Nov;144(2):353-60. doi: 10.1042/bj1440353.

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Role of the lung in total body clearance of circulating drugs.肺在循环药物全身清除中的作用。
Clin Pharmacokinet. 1979 Sep-Oct;4(5):355-67. doi: 10.2165/00003088-197904050-00002.

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