Lithium ions inhibit function of lowbut not high-affinity muscarinic receptors of murine neuroblastoma cells (clone N1E-115)

Murine neuroblastoma cells (clone N1E-115) possess both high- and low-affinity muscarinic receptors. The low-affinity muscarinic receptor, when stimulated, initiates the formation of cyclic GMP by activating the enzyme guanylate cyclase; whereas stimulation of the high-affinity receptor inhibits prostaglanding E₁-mediated cyclic AMP formation by inhibiting the enzyme adenylate cyclase. We have reported that lithium ion (Li⁺) inhibits cyclic GMP formation mediated by the muscarinic receptor agonist, carbachol. in a concentration-dependent manner and that neither ammonium nor sodium ions have such an effect. We extended this study to show that Li⁺ was an apparently noncompetitive inhibitor of the low-affinity muscarinic receptor with an IC₅₀ (±SEM)=13.6±0.8 mM. In addition, Li⁺ with a similar IC₅₀ inhibited the cyclic GMP response in intact cells to sodium azide, which is thought to stimulate guanylate cyclase directly. Moreover, though Li⁺ was found to have a slight inhibitory effect on prostaglandin E₁-stimulated cyclic AMP formation (15% inhibition at 10 mM), it had no effect on the function of the high-affinity muscarinic receptor in intact murine neuroblastoma cells.