Lithium inhibition of forskolin-stimulated adenylate cyclase

The lithium sensitivity of forskolin- and fluoride-stimulated adenylate cyclase activity was investigated in rat brain homogenates in vivo and in vitro. The unstimulated and fluoride-stimulated activity was not affected by lithium, while the forskolin stimulation exhibited a pronounced inhibition by this cation. Furthermore, if Mn2+ was substituted for Mg2+ in the assay media, the forskolin-stimulated activity was even more sensitive to lithium. The results indicate an action of lithium mainly on the catalytic moiety in the adenylate cyclase system. However, the effect cannot be direct on this protein, since the unstimulated activity was unaffected. The action is rather on the microenvironment surrounding this protein, thereby interfering with a possible conformational change of the adenylate cyclase of importance for the activation of this enzyme.