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

Abstract

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.

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Correspondence to Elliott Richelson.

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Kanba, S., Pfenning, M. & Richelson, E. Lithium ions inhibit function of lowbut not high-affinity muscarinic receptors of murine neuroblastoma cells (clone N1E-115). Psychopharmacology 86, 413–416 (1985). https://doi.org/10.1007/BF00427901

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Key words

  • Lithium ion
  • Muscarinic acetylcholine receptor
  • Prostaglandin E1 receptor
  • Cyclic GMP
  • Cyclic AMP
  • Guanylate cyclase