“抗痴呆药物”泛酰 -γ-氨基丁酸对大鼠脑内胆碱高亲和力转运以及胆碱和乙酰胆碱含量的影响

Effect of the 'antidementia drug' pantoyl-GABA on high affinity transport of choline and on the contents of choline and acetylcholine in rat brain.

Nakahiro M, Mochizuki D, Uchida S, Yoshida H

Department of Pharmacology I, Osaka University School of Medicine, Japan.

Br J Pharmacol. 1988 Dec;95(4):1303-7. doi: 10.1111/j.1476-5381.1988.tb11768.x.

Abstract

Effect of pantoyl-gamma-aminobutyric acid (pantoyl-GABA) on high affinity transport of choline into synaptosomes and on the choline (Ch) and acetylcholine (ACh) concentrations of rat brain were studied. 2. Pantoyl-GABA was injected intraperitoneally four times at a dose of 500 mg kg-1 at intervals of 30 min. One hour after the last injection, rats were killed by decapitation for measurement of high affinity transport of Ch into synaptosomes or by microwave irradiation for the measurement of Ch and ACh concentrations. 3. Transport of Ch was increased into synaptosomes prepared from the cerebral cortex and hippocampus, but not into those from the striatum. 4. In the cerebral cortex and hippocampus, Ch concentration was increased and ACh concentration decreased. 5. Since treatments that enhance the activity of cholinergic neurones in vivo are reported to increase high affinity transport of Ch measured in vitro, the present results suggest that pantoyl-GABA may increase cholinergic activity in vivo. This action of the drug may be related to changes in the Ch and ACh concentrations.

摘要

研究了泛酰-γ-氨基丁酸（泛酰-GABA）对胆碱向突触体高亲和力转运以及对大鼠脑内胆碱（Ch）和乙酰胆碱（ACh）浓度的影响。2. 以500 mg kg-1的剂量，每隔30分钟腹腔注射泛酰-GABA 4次。末次注射1小时后，断头处死大鼠以测定胆碱向突触体的高亲和力转运，或用微波辐照法测定胆碱和乙酰胆碱浓度。3. 从大脑皮层和海马制备的突触体中胆碱的转运增加，但从纹状体制备的突触体中则未增加。4. 在大脑皮层和海马中，胆碱浓度升高而乙酰胆碱浓度降低。5. 由于据报道，在体内增强胆碱能神经元活性的处理会增加体外测定的胆碱高亲和力转运，因此本研究结果提示泛酰-GABA可能在体内增加胆碱能活性。该药物的这一作用可能与胆碱和乙酰胆碱浓度的变化有关。