Receptor coupling to G proteins: Interactions not affected by lithium

Receptor-G protein interactions were evaluated according to the abilities of GTP analogs to modulate the affinities of receptor agonists and the abilities of agonists to enhance the dissociation of bound GTPγS. Such interactions were readily observed for α₂ adrenergic receptors (platelets) and muscarinic receptors (heart, brainstem, hippocampus, and CHO-K1 cells expressing the m2 subtype). It has been reported that lithium abolishes receptor-G protein communication, but the presence of lithium at and above clinically relevant concentrations did not alter any of these interactions in our studies. In light of these data, investigators should not assume that lithium can be used to evaluate G protein involvement in cellular functions.