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 (IC50 s 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.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D008094:Lithium / Q000494:pharmacology*; D051379:Mice; D009496:Neurotensin / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors
D010726:Phosphodiesterase Inhibitors; D000804:Angiotensin II; D009496:Neurotensin; D008094:Lithium; D006152:Cyclic GMP; D001920:Bradykinin