Abstract

The effect of lithium on the phosphoinositide-signaling pathway was examined in 5-HT_2C receptors, which are involved in phospholipase C stimulation, expressed in Xenopus laevisoocytes by voltage-clamp recording and assay of intracellular Ca²⁺ concentrations. Treatment with lithium for 60 sec after the initial application of 5-HT reduced Ca²⁺-dependent chloride currents in a dose-dependent manner (0.01–1 mm) and inhibited intracellular Ca²⁺release, whereas pretreatment with lithium or injection into oocytes had no effect. Additionally, treatment with lithium for more than 24 hr reduced 5-HT-evoked currents to a much lesser extent. In contrast, the currents through other phosphoinositide-dependent receptors, such as endogenous “serum” and muscarinic ACh receptors, were not affected or less affected by a short term or long term treatment with lithium, respectively. These results indicate that lithium may have a specific blocking effect on the 5-HT_2C receptors and, in part, nonselectively act on the phosphoinositide metabolic pathway.