The Effect of Lithium on Unstimulated and Glucagon-stimulated Urinary Cyclic AMP Excretion in Rat and Man

The purpose of this study was to determine whether lithium also inhibits hormone-stimulated adenylate cyclase in vivo. The effect of long-term lithium treatment on unstimulated and glucagon-stimulated cyclic AMP excretion was studied in the rat and in man. The influence of lithium on plasma glucagon degradation was also investigated. It was found that in the rat lithium doubled unstimulated and glucagon-stimulated urinary cyclic AMP excretion. In lithium treated rats plasma glucagon concentrations thirty minutes after intraperitoneal injection were twice that of the control rats. In man, lithium affected neither cyclic AMP excretion nor glucagon degradation. These results offer no support for the hypothesis that in vivo lithium in general inhibits hormone-stimulated adenylate cyclase. However, in the intact organism lithium may have additional pharmacological actions, and complex regulatory mechanisms which may modify the cyclic AMP metabolism. Therefore it may be premature to conclude that lithium per se does not have an inhibitory action on glucagon-sensitive adenylate cyclase in vivo.