Nicotinic acetylcholine receptor-mediated neuroprotection by donepezil against glutamate neurotoxicity in rat cortical neurons.
The effect of chronic treatment with the cholinesterase inhibitor tacrine on nicotinic receptor subtypes was investigated in human SH-SY5Y neuroblastoma cells and in a fibroblast cell line (M10 cells) stably transfected with alpha4beta2 nicotinic receptors. Tacrine significantly increased the number of nicotinic receptors in SH-SY5Y cells, in a concentration dependent manner (10(-9) to 10(-4) M), when using [3H]epibatidine as labelled ligand. Chronic tacrine treatment of M10 cells significantly increased and decreased the number of alpha4beta2 nicotinic receptors in a concentration dependent manner (10(-9) to 5 x 10(-6) M and 2 x 10(-5) to 10(-4) M, respectively). The tacrine induced increase of nicotinic receptors in SH-SY5Y cells, was not blocked in the presence of the nicotinic antagonists tubocurarine or mecamylamine. A further increase in the number of nicotinic receptors was, however, observed in the presence of mecamylamine. This study demonstrates that the effect of tacrine on the number of nicotinic receptor subtypes is different in human SH-SY5Y neuroblastoma and M10 cells. The up-regulation of different nicotinic receptor subtypes obtained with tacrine might be achieved through interaction via different binding sites on the receptor, i.e. the acetylcholine binding site as well as an allosteric site.