Effect of Li+ upon the Mg2+-Dependent Activation of Recombinant Giα1
2001
Abstract Although lithium salts have been used in the treatment and prophylaxis of manic-depressive or bipolar patients for 50 years, the mechanism of the pharmacologic action of Li + is unknown. Based on activity studies of inhibitory and stimulatory guanine-binding (G) proteins in rat cortical membranes, it was proposed that Li + inhibition of G-proteins may account for its pharmacologic action. We used the purified α subunit of the recombinant inhibitory G-protein, rG iα1 , and found that Li + at therapeutic levels significantly inhibited the formation of the GDP.AlF − 4 .rG iα1 complex. Because our studies were conducted with a purified, metal-reconstitutedG-protein rather than with cell membrane suspensions, our Li + inhibition results lend additional support to the G-protein hypothesis for Li + action.
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