Erhardt S, Oberg H, Mathé J M, Engberg G
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Amino Acids. 2001;20(4):353-62. doi: 10.1007/s007260170032.
Inhibitors of kynurenine 3-hydroxylase have previously been used to increase endogenous levels of kynurenic acid, an excitatory amino acid receptor antagonist. In the present electrophysiological study PNU 156561A was utilized to elevate endogenous concentrations of kynurenic acid and subsequent effects on the firing pattern of dopamine (DA) neurons of rat substantia nigra (SN) were analyzed. Pretreatment with PNU 156561A (40 mg/kg, i.v., 5-7 h) caused a five-fold increase in endogenous kynurenic acid levels in whole brain five to seven hours after administration and also evoked a significant increase in firing rate and bursting activity of nigral DA neurons. The results of the present study show that a moderate increase in endogenous kynurenic acid levels produces significant actions on the tonic glutamatergic control of the firing pattern of nigral DA neurons, and implicate kynurenine 3-hydroxylase inhibitors as novel antiparkinsonian agents.
犬尿氨酸3-羟化酶抑制剂此前已被用于提高内源性犬尿喹啉酸水平，犬尿喹啉酸是一种兴奋性氨基酸受体拮抗剂。在当前的电生理学研究中，使用PNU 156561A提高内源性犬尿喹啉酸浓度，并分析其对大鼠黑质多巴胺（DA）能神经元放电模式的后续影响。用PNU 156561A（40mg/kg，静脉注射，5 - 7小时）预处理，在给药后5至7小时使全脑内源性犬尿喹啉酸水平增加了五倍，同时也引起黑质DA能神经元放电频率和爆发活动显著增加。本研究结果表明，内源性犬尿喹啉酸水平适度增加对黑质DA能神经元放电模式的紧张性谷氨酸能控制产生显著作用，并表明犬尿氨酸3-羟化酶抑制剂作为新型抗帕金森病药物。
