On the Mechanism of Inhibition of Rat Fat Cell Adenylate Cyclase by Lithium

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Abstract
Li+ is used in the treatment of affective disorders. The mechanism by which Li+ inhibits adenylate cyclase (AC) in vitro was studied. Li+ inhibited the norepinephrine-(NE) and F-stimulated AC activities of rat fat cell ghosts at Li+ concentrations > 10 mM. The basal enzyme activity was unaffected even at 80 mM of Li+. Li+ inhibited NE-induced AC activity in a mainly non-competitive way but the inhibitory effect decreased with increasing concentrations of NE. The inhibition by Li+ of NE- and F-stimulated AC activity was independent of the NE concentration. Ca2+, inhibiting AC activity by a Mg2+ antagonism, abolished the inhibitory effect of Li+. Li+ affected the Ka of NE and the Vmax of AC through an inhibitory action of LiATP3- at the catalytic site of AC or an inhibitory action of Li+ at an allosteric Mg2+ site of AC.