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.Abstract Teaser