Lithium mechanisms in bipolar illness and altered intracellular calcium functions.
Calcium functions as an intracellular second messenger, transducing a variety of hormonal, electrical, and mechanical stimuli by activating a wide range of enzymes. There is evidence, ranging from definitive to strongly presumptive in quality, that lithium can alter many calcium-dependent processes. The list of enzyme systems dependent on calcium and altered by lithium includes adenylate cyclase, glycogen synthase, inositol-1-phosphatase, and calcium adenosine triphosphatase (ATPase). Lithium also interferes with calcium regulation of receptor sensitivity, parathyroid hormone release, microtubule structure, and other systems. All of the neural mechanisms that are hypothesized to explain various psychopharmacological treatments of bipolar illness involve functions that are critically controlled by calcium. Moreover, in every instance, a known action of lithium on calcium function could account for lithium's therapeutic or prophylactic results. From these considerations the dual hypotheses emerge that bipolar illnesses arise from disorders in calcium-regulated functions and that lithium acts by reversing or counterbalancing the effects of these calcium dysfunctions.
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D000262:Adenylyl Cyclases / Q000378:metabolism; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000201:enzymology; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006006:Glycogen Synthase / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D008094:Lithium / Q000627:therapeutic use*; D008870:Microtubules / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014364:Tryptophan / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007473:Ion Channels; D005680:gamma-Aminobutyric Acid; D014364:Tryptophan; D008094:Lithium; D014446:Tyrosine 3-Monooxygenase; D006006:Glycogen Synthase; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D000262:Adenylyl Cyclases; D000252:Calcium-Transporting ATPases; D002118:Calcium; D009638:Norepinephrine