Maruyama Y, Teraoka H, Iwata H, Kazusaka A, Fujita S
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818 Japan.
Neurochem Int. 2001 Jun;38(7):567-72. doi: 10.1016/s0197-0186(00)00121-2.
Naturally occurring neurotoxins, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines (DHTIQs), thought to be the causative agents of Parkinsonism. DHTIQs including norsalsolinol have been found in the mammalian central nervous system. Norsalsolinol can be formed by a non-enzymatic Pictet-Spengler condensation reaction between dopamine and formaldehyde, and has been detected in the urine of Parkinsonian patients. However, the effects of DHTIQs on the secretion of dopamine, as well as other neurotransmitters, are not well understood. This study investigated the effects of norsalsolinol on dopamine secretion from nerve growth factor-differentiated PC12 cells. Norsalsolinol (1-100 microM) pretreatment suppressed both ATP (100 microM)- and K(+) (50 mM)-induced dopamine secretion from PC12 cells in a concentration-dependent fashion, but did not affect basal dopamine secretion. In beta-escin-permeabilized PC12 cells, norsalsolinol pretreatment suppressed Ca(2+) (pCa=4-8)-induced dopamine secretion, but did not inhibit the secretagogue-induced change in intracellular Ca(2+) concentration. These results suggest that norsalsolinol causes the inhibition of secretagogue-induced dopamine secretion from PC12 cells without altering intracellular Ca(2+) concentration. Inhibition of dopamine secretion by norsalsolinol may also be involved in postural abnormality in Parkinson's disease.
天然存在的神经毒素6,7 - 二羟基 - 1,2,3,4 - 四氢异喹啉（DHTIQs）被认为是帕金森症的致病因子。包括去甲猪毛菜碱在内的DHTIQs已在哺乳动物中枢神经系统中被发现。去甲猪毛菜碱可由多巴胺与甲醛之间的非酶Pictet - Spengler缩合反应形成，并且已在帕金森病患者的尿液中检测到。然而，DHTIQs对多巴胺以及其他神经递质分泌的影响尚未完全清楚。本研究调查了去甲猪毛菜碱对神经生长因子分化的PC12细胞多巴胺分泌的影响。去甲猪毛菜碱（1 - 100 microM）预处理以浓度依赖的方式抑制了ATP（100 microM）和K⁺（50 mM）诱导的PC12细胞多巴胺分泌，但不影响基础多巴胺分泌。在β - 七叶皂苷通透的PC12细胞中，去甲猪毛菜碱预处理抑制了Ca²⁺（pCa = 4 - 8）诱导的多巴胺分泌，但不抑制促分泌剂诱导的细胞内Ca²⁺浓度变化。这些结果表明，去甲猪毛菜碱导致PC12细胞中促分泌剂诱导的多巴胺分泌受到抑制，而不改变细胞内Ca²⁺浓度。去甲猪毛菜碱对多巴胺分泌的抑制作用可能也与帕金森病的姿势异常有关。
