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(+)-苯丙胺、α-甲基酪氨酸和α-甲基苯丙氨酸对大鼠纹状体中间酪氨酸和α-甲基间酪氨酸浓度的影响。

The effects of (+)-amphetamine, alpha-methyltyrosine, and alpha-methylphenylalanine on the concentrations of m-tyramine and alpha-methyl-m-tyramine in rat striatum.

作者信息

Dougan D F, Duffield A M, Duffield P H, Wade D N

出版信息

Br J Pharmacol. 1983 Oct;80(2):309-14. doi: 10.1111/j.1476-5381.1983.tb10035.x.

Abstract

The concentration in rat striatum of the meta and para isomers of tyramine and alpha-methyltyramine, after the administration of (+)-amphetamine, alpha-methyl-p-tyrosine (AMPT) and alpha-methylphenylalanine (AMPA) has been determined using chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Twenty hours after the last of 7 daily injections of (+)-amphetamine (5 mg kg-1 i.p.) the concentration of alpha-methyl-p-tyramine in striatal tissue increased twofold compared to the concentration 20 h after a single injection. In contrast the concentration of alpha-methyl-m-tyramine did not change. alpha-Methyl-m-tyramine and alpha-methyldopamine were found in the striatum at concentrations of 42 ng g-1 and 13.5 ng g-1 respectively after treatment of rats 20 h before with AMPA (100 mg kg-1 i.p.). After treatment with AMPT (100 mg kg-1, 20 h before decapitation) only the para isomer of alpha-methyltyramine could be detected (13.7 ng g-1) although the striatal concentration of alpha-methyldopamine was 274 ng g-1, a level 20 times greater than that observed after AMPA treatment. The combined administration of both AMPT and AMPA (100 mg kg-1 each, 20 h) resulted in a reduction of the striatal concentration of alpha-methyl-m-tyramine but not alpha-methyl-p-tyramine. These data suggest that alpha-methyl-m-tyramine in rat striatum is formed by the enzyme tyrosine hydroxylase on substrate AMPA, rather than by ring dehydroxylation of alpha-methyldopa and alpha-methyldopamine. Significant reductions in the striatal concentrations of m-tyramine 2 h after the administration of AMPT, suggest that tyrosine hydroxylase is involved similarly in the production of m-tyramine.

摘要

运用化学电离气相色谱质谱联用仪(c.i.g.c.m.s.)测定了给予(+)-苯丙胺、α-甲基对酪氨酸(AMPT)和α-甲基苯丙氨酸(AMPA)后,大鼠纹状体中酪胺和α-甲基酪胺的间位和对位异构体的浓度。在每日7次注射(+)-苯丙胺(5mg/kg,腹腔注射)的最后一次注射20小时后,纹状体组织中α-甲基对酪胺的浓度相较于单次注射20小时后的浓度增加了两倍。相比之下,α-甲基间酪胺的浓度没有变化。在用AMPA(100mg/kg,腹腔注射)处理大鼠20小时后,在纹状体中发现α-甲基间酪胺和α-甲基多巴胺的浓度分别为42ng/g和13.5ng/g。在用AMPT(100mg/kg,断头前20小时)处理后,虽然纹状体中α-甲基多巴胺的浓度为274ng/g,是AMPA处理后观察到水平的20倍,但仅能检测到α-甲基酪胺的对位异构体(13.7ng/g)。同时给予AMPT和AMPA(各100mg/kg,20小时)导致纹状体中α-甲基间酪胺的浓度降低,但α-甲基对酪胺的浓度未降低。这些数据表明,大鼠纹状体中的α-甲基间酪胺是由酪氨酸羟化酶作用于底物AMPA形成的,而不是由α-甲基多巴和α-甲基多巴胺的环脱羟基作用形成的。给予AMPT 2小时后,纹状体中间酪胺的浓度显著降低,这表明酪氨酸羟化酶同样参与了间酪胺的生成。

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