Lack of Interfering Effects of Lithium on Receptor/G Protein Coupling in Human Platelet and Rat Brain Membranes

To verify the theory that lithium exerts its multiple effects by altering the receptor-mediated G proteinʹs activation, in vitro effects of lithium on agonist-induced guanosine triphosphate (GTP) hydrolysis were examined. The basal GTP hydrolyzing activity in human platelet membranes was decreased nonselectively by either LiCl or NaCl at millimolar concentrations, whereas (−)-epinephrine-stimulated increase in the activity (an index of α2A-adrenoceptor coupled Gi2 function) was unaltered. Furthermore, the stimulation of high-affinity GTPase activity induced by dopamine, carbachol, and R-N6-phenylisopropyladenosine in rat brain membranes (indices of the functional coupling between dopamine D2-like, pirenzepine-insentive muscarinic, and adenosine A1 receptors and their respective Gi proteins) was substantially unaltered regardless of whether 0.5 mmol/L adenosine 5′-(β, γ-imido)triphosphate (i.e., 1.75 mmol/L lithium) was included in the assay mixture or not. These results indicate that lithium does not affect in vitro the receptor-mediated activational process of G proteins, at least not of Gi associated with adenylate cyclase inhibition.