Lithium suppresses signaling and induces rapid sequestration of beta 2-adrenergic receptors

Lithium is a monovalent cation used therapeutically to treat a range of aff ective disorders (1), although the cellular mechanisms of lithium regulatio n that might contribute to its therapeutic effects at the level of neurotra nsmitter receptors are not known. Herein we report the ability of lithium t o stimulate the internalization of beta2-adrenergic receptors. Lithium trea tment of A431 human epidermoid carcinoma cells resulted in a rapid, promine nt desensitization and internalization of beta2-adrenergic receptors. The a bility of these receptors to generate a cyclic AMP response was strongly in hibited by lithium, at concentrations therapeutic in humans. Receptors for the serotonin (5HT1c) and for opiates mu -opioid), in sharp contrast, resis ted the effects of lithium on internalization. These data provide the first receptor-based mechanism to be described for lithium that could explain, i n part, the therapeutic effects of lithium on affective disorders. (C) 2001 Academic Press.