Alteration in the regulation of neuronal muscarinic acetylcholine receptor number induced by chronic lithium in neuroblastoma cells.

Because previous studies in whole-animal models have reported inconsistent results regarding the effect of chronic lithium on the regulation of the neuronal muscarinic acetylcholine receptor (mAChR) number, we examined the effect of chronic lithium on the regulation of mAChR in cell cultures of N1E-115, a mouse neuroblastoma clone. Li+ induced a concentration- and time-dependent increase in the mAChR number, with a 30% increase in specific [3H]quinuclidinyl benzilate binding in membrane homogenates induced by a 5-day incubation with 10 mM Li+. Agonist-induced down-regulation of the mAChR number was also inhibited by lithium: chronic treatment with 10 mM Li+ caused a 25-35% reduction in the magnitude of carbachol. In contrast, the decrease in the mAChR number induced by the synergistic action of A23187 (300 nM) and phorbol myristate acetate (300 nM) was unaffected by Li+. These results demonstrate that chronic treatment with Li+ increases the basal mAChR number and dampens the decrease in receptor number induced by a muscarinic agonist in neuroblastoma cells. The implications of these results in understanding the functional regulation of neuronal mAChR number are discussed.