基础状态及哌泊噻嗪激活后，脑内多巴胺能区域的游离及结合型3,4-二羟基苯乙酸和高香草酸

Free and conjugated 3,4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation.

作者信息

Tavitian E, Peyrin L, Dalmaz Y, Favre R, De Haut M, Cottet-Emard J M

出版信息

J Neural Transm. 1986;65(3-4):261-75. doi: 10.1007/BF01249087.

Abstract

We have determined free and conjugated 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in discrete brain areas of rats. Conjugated HVA or DOPAC accounted for 22-38% of total acids in striatum, mesolimbic tissue or prefrontal cortex. Activation of dopamine (DA) metabolism by a single injection of pipotiazine palmitic ester (PPZ), a long-lasting neuroleptic, increased free acid levels (DOPAC and HVA) at either dose and conjugate levels after 32 or 50 mg/kg. 48 hours after PPZ-32 mg/kg, the observed increases of conjugates could exceed in some cases those of corresponding free acids. About half of total DOPAC and HVA were conjugated in hypothalamus, PPZ moderately increased free DOPAC (at 32 mg/kg) but did not elevate significantly the conjugated form. It is concluded that sulfation is an important pathway for DOPAC and HVA metabolism in brain and that the determination of both free and conjugated DOPAC or/and HVA may shed additional lights on regional DA metabolism and the effect of drugs thereon.

摘要

我们已测定了大鼠离散脑区中的游离型和结合型3,4 - 二羟基苯乙酸（DOPAC）和高香草酸（HVA）。结合型HVA或DOPAC在纹状体、中脑边缘组织或前额叶皮质中占总酸的22 - 38%。单次注射长效抗精神病药物哌泊噻嗪棕榈酸酯（PPZ）激活多巴胺（DA）代谢后，无论剂量高低，游离酸水平（DOPAC和HVA）均升高，32或50 mg/kg剂量下结合物水平也升高。PPZ 32 mg/kg给药48小时后，观察到的结合物增加在某些情况下可能超过相应游离酸的增加。下丘脑约一半的总DOPAC和HVA是结合型的，PPZ适度增加游离DOPAC（32 mg/kg时），但未显著提高结合型。结论是，硫酸化是脑中DOPAC和HVA代谢的重要途径，游离型和结合型DOPAC或/和HVA的测定可能为区域DA代谢及其药物效应提供更多线索。