Influence of lithium on cyclic AMP accumulation in isolated rat fat cells

Lithium inhibits in vitro as well as in vivo several hormone-stimulated adenylate cyclases. The aim of this study was to investigate the mechanism by which lithium inhibits adenylate cyclase in vitro. It was found that lithium inhibited both the norepinephrine- and the glucagon-induced cAMP accumulation in rat fat cells at lithium concentrations above 10 mM. The basal cAMP content was unaffected even at 40 mM of lithium. The inhibitory action was time-dependent and reversible, indicating an intracellular site of action. Lithium inhibited both norepinephrine- and glucagon-stimulated cAMP accumulation in a mainly non-competitive way, but the inhibitory effect decreased with increasing hormone concentrations. In accordance, lithium and propranolol had a supraadditive effect on norepinephrine-induced cAMP accumulation. It is suggested that lithium affects both the hormone-receptor binding as well as the transfer of the hormonal stimulus by an intracellular site of action.