Lithium suppresses signaling and induces rapid sequestration of beta2-adrenergic receptors.
Lithium is a monovalent cation used therapeutically to treat a range of affective disorders (1), although the cellular mechanisms of lithium regulation that might contribute to its therapeutic effects at the level of neurotransmitter receptors are not known. Herein we report the ability of lithium to stimulate the internalization of beta2-adrenergic receptors. Lithium treatment of A431 human epidermoid carcinoma cells resulted in a rapid, prominent desensitization and internalization of beta2-adrenergic receptors. The ability of these receptors to generate a cyclic AMP response was strongly inhibited by lithium, at concentrations therapeutic in humans. Receptors for the serotonin (5HT1c) and for opiates (mu-opioid), in sharp contrast, resisted the effects of lithium on internalization. These data provide the first receptor-based mechanism to be described for lithium that could explain, in part, the therapeutic effects of lithium on affective disorders.
Doronin
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S
Department of Molecular Pharmacology, University Medical Center, SUNY/Stony Brook, NY 11794-8651, USA.
Shumay
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Wang
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HY
Malbon
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CC
D058672:Adrenergic beta-2 Receptor Antagonists; D018692:Antimanic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004705:Endocytosis; D006801:Humans; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D058672:Adrenergic beta-2 Receptor Antagonists; D018692:Antimanic Agents; D018343:Receptors, Adrenergic, beta-2; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D008094:Lithium; D000242:Cyclic AMP