Influence of Lithium on Cyclic AMP Accumulation in Isolated Rat Fat Cells

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Abstract
Li inhibits in vitro as well as in vivo several hormone-stimulated adenylate cyclases. The mechanism by which Li inhibits adenylate cyclase in vitro was investigated. Li inhibited both the norepinephrine- and the glucagon-induced cyclic [c]AMP accumulation in rat fat cells at Li concentrations above 10 mM. The basal cAMP content was unaffected even at 40 mM of Li. The inhibitory action was time-dependent and reversible, indicating an intracellular site of action. Li inhibited both norepinephrine- and glucagon-stimulated cAMP accumulation in a mainly non-competitive way, but the inhibitory effect decreased with increasing hormone concentrations. Li and propranolol had a supraadditive effect on norepinephrine-induced cAMP accumulation. Li evidently affects both the hormone-receptor binding as well as the transfer of the hormonal stimulus by an intracellular site of action. [Li is used against affective illness.].