Dissociation by Lithium of Hormone-induced Formation of Cyclic AMP and Release of Glycerol in Isolated Rat Fat Cells

It has been suggested that lithium exerts some of its pharmacological actions by inhibition of the membrane-bound enzyme adenylate cyclase. However, the relationship between the lithium inhibition of adenylate cyclase and the corresponding physiological parameters, e.g. lipolysis, has not been investigated. In the present study it was found that lithium inhibited both the norepinephrine-induced accumulation of cAMP and release of glycerol in isolated rat fat cells, but only in the lower dose range of norepinephrine. At maximally effective concentrations of norepinephrine, where in the presence of 40 mM of lithium the formation of cAMP was reduced by approximally 40%, lipolysis remained unaffected. The basal content of cAMP and the basal release of glycerol were not inhibited by lithium. In addition to the inhibitory effect of lithium, lithium was found to stimulate the release of glycerol. This stimulatory effect of lithium may be explained by a prevention by lithium of the feedback inhibition by free fatty acids of adenylate cyclase and/or triglyceride lipase, since it could be avoided by increasing the concentration of bovine serum albumin in the incubation medium. It is concluded that lithium by inhibition of hormone-stimulated adenylate cyclase activity inhibits lipolysis only at submaximal hormone concentrations. This dissociation by lithium of cAMP accumulation and glycerol release may suggest that at least at high concentrations of norepinephrine cAMP-independent factors are involved in lipolysis.