J Neuropsychiatry Clin Neurosci 1993; 5:361-368
Copyright © 1993 by American Neuropsychiatric Association
Is the Na(+)-K(+)-ATPase the link between phosphoinositide metabolism and bipolar disorder?
RS el-Mallakh and R Li
Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, KY 40292-0001.
Recent experimental work suggests involvement of the phosphatidyl inositol
second messenger system in the biochemical mechanism of lithium action, but
this work has not shed light on the pathophysiology of bipolar illness.
Earlier work had established reduction in sodium- potassium-activated
adenosine triphosphatase (Na(+)-K(+)-ATPase) activity as a consistent
marker of mood in bipolar illness but had only partially illuminated
mechanisms of the action of lithium. Now, advances from research in
diabetic neuropathy suggest that inositol phosphate and diacylglycerol
metabolism are indeed linked to Na(+)-K(+)- ATPase activity. The data are
compatible with a model in which a primary decrease in Na(+)-K(+)-ATPase
activity in bipolar patients can stimulate an increase in phosphoinositide
hydrolysis, thereby generating the equivalent of a second messenger signal
in the absence of a first message. Lithium appears to act by blocking this
false second message.
