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Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex

Nature volume 331, pages 440–442 (1988)Cite this article

Abstract

Lithium is a unique drug with therapeutic as well as prophylactic value for both manic and depressive phases of manic-depressive illness,1,2. The precise mechanisms of its clinical efficacy remain unknown, but there are two main theories of its biochemical action. One proposes that lithium inhibits adrenergically activated adenylate cyclase function3–5 whereas the other suggests that it inhibits phosphatidyl inositol turnover, which is known to be activated by cholinergic agonists6–8. Neither mechanism alone, however, can explain both the antimanic and antidepressant effects of lithium. Because of the pivotal role of G proteins in post-receptor information transduction, we have investigated the interaction of lithium with G protein function. Lithium at therapeutically efficacious concentrations completely blocked both adrenergic and cholinergic agonist-induced increases in [3H]GTP binding to membranes from rat cerebral cortex, in both in vitro and ex vivo experiments. The same lithium treatments also abolished guanine nucleotide modulation of agonist binding. Our findings suggest G proteins (Gs and Gj or G0) as the molecular site of action for both the antimanic and antidepressant effects of lithium.

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Authors and Affiliations

  1. Clinical Pharmacology Unit, Ben Gurion University of the Negev, P.O.B. 4600, Beer Sheva, Israel

    Sofia Avissar & Abraham Danon

  2. Beer Sheva Mental Health Center, Ida and Solomon Stern Psychiatry Research Unit, Ben Gurion University of the Negev, P.O.B. 4600, Beer Sheva, Israel

    Gabriel Schreibert & R.H. Belmaker

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  1. Sofia Avissar
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  2. Gabriel Schreibert
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  3. Abraham Danon
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  4. R.H. Belmaker
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Avissar, S., Schreibert, G., Danon, A. et al. Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex. Nature 331, 440–442 (1988). https://doi.org/10.1038/331440a0

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