Figure 334

The actions of Li+ on postsynaptic receptor-mediated second-messenger signaling systems. Lithium can simultaneously alter the flow of synaptic information through several receptor-mediated systems by diminishing coupling between the receptor recognition site and its specific G proteins. This model explains the stabilizing actions of Li+ at both ends of the mood spectrum through a single action at the G-protein level. Attenuating actions of Li+ have been demonstrated through G-protein interactions at the p-adrenoceptor and the acetylcholine M1 muscarinic receptor systems of the CNS. A second action of Li+ as an inhibitor of inositol diphosphate (IP2) phosphatase may further attenuate the flow of synaptic information through the M1 muscarinic receptor by the eventual depletion of membrane phosphatidyl inositol-bis-phosphate (PIP2). IP3, inositol triphosphate; DAG, diacylglycerol; ATP adenosine triphosphate; cAMP cyclic adenosine monophosphate; 5'-AMP 5'-adenosine monophosphate; NE, norepinephrine; ACh, acetylcholine.

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