ANTICHOLINESTERASIC DRUGS - TACRINE BUT NOT PHYSOSTIGMINE, ACCUMULATES IN ACIDIC COMPARTMENTS OF THE CELLS
ANTICHOLINESTERASIC DRUGS - TACRINE BUT NOT PHYSOSTIGMINE, ACCUMULATES IN ACIDIC COMPARTMENTS OF THE CELLS
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DOI：
10.1016/0925-4439(94)00079-6
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发表时间：
1995-04-24
影响因子：
6.2
通讯作者：
ZATTA, P
中科院分区：
文献类型：
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作者：
DELLATONE, P;BRAGADIN, M;ZATTA, P
他克林（THA）和毒扁豆碱（PHS）因其抗胆碱酯酶活性而被用于阿尔茨海默病的治疗。在这里，我们表明THA以能量依赖性方式在大鼠溶酶体中被吸收，并且它也在大鼠胸腺细胞和神经母细胞瘤细胞的酸性隔室中积累。在所有上述体外系统中，小于1 mM的THA浓度消除了pH梯度（Δ pH）。相反，较高浓度的PHS（1-2 mM）无效。THA在细胞酸性细胞器中的积累可能与THA在阿尔茨海默病治疗中的药理作用有关。
Tacrine (THA) and physostigmine (PHS) have been used in Alzheimer's disease therapy for their anticholinesterasic activity. Here we show that THA is taken up in rat lysosomes in an energy-dependent manner, and that it is also accumulated in acidic compartments of rat thymocytes and neuroblastoma cells. A concentration of THA less than 1 mM dissipated the pH gradient (Delta pH) in all the above mentioned in vitro systems. On the contrary higher concentrations of PHS (1-2 mM) were ineffective. The accumulation of THA in acidic organelles of the cell may be relevant for the pharmacological action of THA in Alzheimer's treatment.