Lithium administration modulates platelet Gi in humans.

Platelet G proteins were assessed in 7 normal volunteers before and after 14 days of lithium administration at therapeutic plasma levels. Cholera and pertussis toxin catalyzed ADP-ribosylation of platelet membrane proteins were measured by SDS-PAGE. Immunoblotting with specific antibodies was used to measure platelet membrane alpha i content. There was a statistically significant 37% increase in pertussis toxin mediated ADP-ribosylation of a 40,000 Mr protein in platelet membranes after lithium administration, but cholera toxin mediated ADP-ribosylation of a 45,000 Mr protein and alpha i immunoblotting were unchanged by lithium. Increased pertussis toxin stimulated ADP-ribosylation in the absence of changes in alpha i content could be explained by a shift in platelet Gi in favor of its undissociated, inactive form. This would be consistent with increased platelet adenylyl cyclase activity found in these same subjects after lithium.