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家兔离体心脏中外源性和内源性去甲肾上腺素的代谢

Metabolism of endogenous and exogenous noradrenaline in the rabbit perfused heart.

作者信息

Majewski H, Hedler L, Steppeler A, Starke K

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1982 May;319(2):125-9. doi: 10.1007/BF00503924.

DOI:10.1007/BF00503924
PMID:7110374
Abstract

The outflow of noradrenaline, 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) from rabbit perfused hearts was studied by chromatography on alumina followed by high pressure liquid chromatography with electrochemical detection. In the absence of drugs and without nerve stimulation, the outflow of endogenous noradrenaline over a period of 108 min averaged 0.17 pmol X g-1 X min-1 and the outflow of DOPEG 2.1 pmol X g-1 X min-1. The outflow of DOMA was below the detection limit (less than 0.13 pmol X g-1 X min-1). The effect of perfusion with (-)-noradrenaline 0.1, or 10 mumol/l for 18 min was then investigated. As the concentration of nor-adrenaline increased so did the outflow of DOPEG. Moreover, DOMA was found in the venous effluent during and after perfusion with noradrenaline 1 or 10 mumol/l. The increase in the outflow of DOPEG and DOMA was almost abolished when cocaine 10 mumol/l was present during the perfusion with noradrenaline 1 mumol/l. The release of endogenous noradrenaline by sympathetic nerve stimulation or tyramine 10 mumol/l, but not the release evoked by nicotine 30 mumol/l, was accompanied by an increase in the outflow of DOPEG; an outflow of DOMA was not observed. It is concluded that, in the rabbit perfused heart, DOPEG is an important metabolite of endogenous noradrenaline. DOMA is at best a minor product, either when the neurones are at rest or when noradrenaline is released by sympathetic nerve stimulation, nicotine or tyramine. DOMA is formed in detectable amounts when the tissue is exposed to a high concentration of exogenous noradrenaline. Like DOPEG, it is formed intraneuronally. The results confirm and extend those obtained previously on guinea-pig incubated atria. They make it unlikely that, in these tissues at least, DOMA formation is one of the physiological pathways of noradrenaline catabolism.

摘要

采用氧化铝柱色谱法,随后进行带电化学检测的高压液相色谱法,研究了兔离体灌注心脏中去甲肾上腺素、3,4 - 二羟基苯乙二醇(DOPEG)和3,4 - 二羟基扁桃酸(DOMA)的流出情况。在无药物且无神经刺激的情况下,108分钟内内源性去甲肾上腺素的平均流出量为0.17 pmol·g⁻¹·min⁻¹,DOPEG的流出量为2.1 pmol·g⁻¹·min⁻¹。DOMA的流出量低于检测限(小于0.13 pmol·g⁻¹·min⁻¹)。接着研究了用0.1、1或10 μmol/L的( - ) - 去甲肾上腺素灌注18分钟的效果。随着去甲肾上腺素浓度的增加,DOPEG的流出量也增加。此外,在用1或10 μmol/L去甲肾上腺素灌注期间及之后,在静脉流出液中发现了DOMA。当在灌注1 μmol/L去甲肾上腺素期间加入10 μmol/L可卡因时,DOPEG和DOMA流出量的增加几乎被消除。交感神经刺激或10 μmol/L酪胺引起的内源性去甲肾上腺素释放,而非30 μmol/L尼古丁引起的释放,伴随着DOPEG流出量的增加;未观察到DOMA的流出。结论是,在兔离体灌注心脏中,DOPEG是内源性去甲肾上腺素的重要代谢产物。无论是神经元处于静息状态时还是交感神经刺激、尼古丁或酪胺释放去甲肾上腺素时,DOMA充其量只是次要产物。当组织暴露于高浓度外源性去甲肾上腺素时,可检测到DOMA的形成。与DOPEG一样,它在神经元内形成。这些结果证实并扩展了先前在豚鼠离体心房上获得的结果。它们表明,至少在这些组织中,DOMA的形成不太可能是去甲肾上腺素分解代谢的生理途径之一。

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本文引用的文献

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A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines.一项关于影响用于儿茶酚胺分析的氧化铝 - 三羟基吲哚法的因素的研究。
J Pharmacol Exp Ther. 1962 Dec;138:360-75.
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[Noradrenalin loss from the isolated rabbit heart following sympathetic nerve irritation and its pharmacological alteration].[交感神经刺激后离体兔心脏去甲肾上腺素的释放及其药理学改变]
Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1962;244:81-96.
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Mechanism of noradrenaline release from rabbit atria induced by nicotinic agonists.
The determination of presynaptic pA2 values of yohimbine and phentolamine on the perfused rat heart under conditions of negligible autoinhibition.
在自身抑制可忽略不计的条件下,测定育亨宾和酚妥拉明对灌注大鼠心脏的突触前pA2值。
Br J Pharmacol. 1983 May;79(1):109-19. doi: 10.1111/j.1476-5381.1983.tb10502.x.
4
The activity of the neuronal and extraneuronal catecholamine-metabolizing enzymes of the perfused rat heart.灌注大鼠心脏的神经元和非神经元儿茶酚胺代谢酶的活性
Naunyn Schmiedebergs Arch Pharmacol. 1987 Aug;336(2):139-47. doi: 10.1007/BF00165797.
5
The K+-induced increases in noradrenaline and dopamine release are accompanied by reductions in the release of their intraneuronal metabolites from the rat anterior hypothalamus. An in vivo brain microdialysis study.钾离子诱导的去甲肾上腺素和多巴胺释放增加,同时伴随着大鼠下丘脑前部神经元内代谢产物释放的减少。一项体内脑微透析研究。
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):54-9. doi: 10.1007/BF00165126.
6
Neuropeptide Y differentiates between exocytotic and nonexocytotic noradrenaline release in guinea-pig heart.神经肽Y可区分豚鼠心脏中胞吐性和非胞吐性去甲肾上腺素的释放。
Naunyn Schmiedebergs Arch Pharmacol. 1989 Nov;340(5):509-15. doi: 10.1007/BF00260605.
7
The heterogeneity of the neuronal distribution of exogenous noradrenaline in the rat vas deferens.外源性去甲肾上腺素在大鼠输精管中神经元分布的异质性。
Naunyn Schmiedebergs Arch Pharmacol. 1990 Aug;342(2):160-70. doi: 10.1007/BF00166959.
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An analysis of the effects of amezinium on postganglionic sympathetic neurones.阿美铵对节后交感神经元作用的分析。
Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):1-11. doi: 10.1007/BF00498425.
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Med Biol. 1974 Dec;52(6):372-83.
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