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喹啉酸:左旋多巴和利血平给药期间对脑儿茶酚胺和环磷酸腺苷含量的影响。

Quinolinic acid: effects on brain catecholamine and c-AMP content during L-dopa and reserpine administration.

作者信息

Beskid M, Finkiewicz-Murawiejska L

机构信息

Medical Centre of Postgraduate Education, Department of Cell Pathophysiology, Warsaw, Poland.

出版信息

Exp Toxicol Pathol. 1992 Apr;44(2):66-9. doi: 10.1016/S0940-2993(11)80189-2.

Abstract

The catecholamine content in rat brain tissue was determined following the administration of quinolinic acid alone or combined either with L-dopa and decarboxylase inhibitor or reserpine. Quinolinic acid alone decreased the levels of dopamine and noradrenaline, as well as those of c-AMP, and increased those of adrenaline. Treatment with L-dopa/decarboxylase inhibitor reversed the suppressing effect of quinolinic acid on dopamine, but not on noradrenaline. Reserpine alone depleted the contents of dopamine, noradrenaline and adrenaline. It could be concluded from the effects of quinolinic acid and reserpine given together that quinolinic acid suppresses the depletion of amines induced by reserpine. It has been demonstrated that quinolinic acid leads to injuries of nerve-cell bodies in pars compacta of the substantia nigra and in the striatum. Quinolinic acid is a natural metabolite of tryptophan, normally occurring in the liver, kidney and brain (Wolfensberger et al. 1983; Moroni et al. 1984). This compound exhibits convulsant and neuron excitant properties (Stone et al. 1987). It induces a selective pattern of neuronal degeneration both at the site of intracerebral injection (Schwarcz et al. 1983; Stone et al. 1987) and after general (intracardiac) administration (Beskid and Markiewicz 1988). The ability of quinolinic acid to produce neurotoxicity was greater in the striatum than in other parts of the brain. This prompted us to study catecholamine and c-AMP levels in rat brain tissue following quinolinic acid and L-dopa administration, as well as the influence of reserpine on quinolinic acid action.

摘要

单独给予喹啉酸或使其与左旋多巴及脱羧酶抑制剂联合使用,或与利血平联合使用后,测定大鼠脑组织中的儿茶酚胺含量。单独使用喹啉酸可降低多巴胺和去甲肾上腺素水平以及环磷酸腺苷(c-AMP)水平,并升高肾上腺素水平。用左旋多巴/脱羧酶抑制剂进行治疗可逆转喹啉酸对多巴胺的抑制作用,但对去甲肾上腺素无此作用。单独使用利血平可耗尽多巴胺、去甲肾上腺素和肾上腺素的含量。从喹啉酸和利血平共同给药的效果可以得出结论,喹啉酸可抑制利血平诱导的胺类耗竭。已经证明,喹啉酸会导致黑质致密部和纹状体中的神经细胞体受损。喹啉酸是色氨酸的天然代谢产物,正常情况下存在于肝脏、肾脏和大脑中(沃尔芬斯贝格等人,1983年;莫罗尼等人,1984年)。该化合物具有惊厥和神经元兴奋特性(斯通等人,1987年)。它在脑内注射部位(施瓦茨等人,1983年;斯通等人,1987年)以及全身(心内)给药后(贝斯基德和马尔凯维奇,1988年)都会诱导选择性的神经元变性模式。喹啉酸产生神经毒性的能力在纹状体中比在大脑其他部位更强。这促使我们研究喹啉酸和左旋多巴给药后大鼠脑组织中的儿茶酚胺和c-AMP水平,以及利血平对喹啉酸作用的影响。

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