IS THE NA-K+-ATPASE THE LINK BETWEEN PHOSPHOINOSITIDE METABOLISM AND BIPOLAR DISORDER()

Recent experimental work suggests involvement Of the phosphatidyl inos itol second messenger system in the biochemical mechanism of lithium a ction, but this work has not shed light on the pathophysiology of bipo lar illness. Earlier work had established reduction in sodium-potassiu m-activated adenosine triphosphatase (Na+-K+-ATPase) activity as a con sistent marker of mood in bipolar illness but had only partially illum inated mechanisms of the action of lithium. Now, advances from researc h in diabetic neuropathy suggest that inositol phosphate and diacylgly cerol metabolism are indeed linked to Na+-K+-ATPase activity. The data are compatible with a model in which a primary decrease in Na+-K+-ATP ase activity in bipolar patients can stimulate an increase in phosphoi nositide hydrolysis, thereby generating the equivalent of a second mes senger signal in the absence of a first message. Lithium appears to ac t by blocking this false second message.