Lithium ions have a potent and selective inhibitory effect on cyclic GMP formation stimulated by neurotensin, angiotensin II and bradykinin

The effect of lithium ion (Li⁺) on receptor-mediated synthesis of cyclic GMP, a putative second messenger, was examined using intact murine neuroblastoma cells (clone N1E-115). Lithium chloride potently inhibited cyclic GMP formation stimulated by the neuropeptides, neurotensin, angiotensin II and bradykinin in an identical concentration-dependent (IC₅₀s of around 12 mM), saturable and reversible manner. In the presence of veratridine, an alkaloid which by stimulating sodium channels can increase Li⁺ entry into the cells, Li⁺ inhibited neurotensin-stimulated cyclic GMP formation more potently (IC₅₀ = 7 mM). No effect of Li⁺ was observed on phosphodiesterase (EC 3.1.4.17) activity. These results suggest that Li⁺ may interfere with the function of these receptors through its inhibitory effect at a common site in the pathway of receptor-mediated cyclic GMP formation.