Alteration in the Regulation of Neuronal Muscarinic Actylcholine Receptor Number Induced by Chronic Lithium in Neuroblastoma Cells

摘要

Although lithium is widely employed as an effective therapeutic agent for the treatment of affective disorders, its precise mechanism of action and effects of neuronal function remain unclear. However, the recent discovery that Li inhibits inositol-1-phosphatase, an important enzyme in the metabolic cycling of phosphatidylinositol (PI), has rekindled interest in the molecular mechanisms underlying the effects of lithium on the CNS. Because Li has been shown to reduce inositol levels in excitable cells several investigators have proposed that chronic Li treatment may dampen the cellular response to neurotransmitters whose receptor systems are linked to the hydrolysis of PI. Insight into the effect of Li on neuronal muscarinic acetylcholine receptor (mAChR) regulation is of particular interest given the possible role of the CNS mAChR system in the pathogenesis of affective illness. 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. Reprints.(kt)