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

Shigenobu Kanba, Michael Pfenning, Elliott Richelson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)413-416
Number of pages4
JournalPsychopharmacology
Volume86
Issue number4
DOIs
StatePublished - Aug 1985

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

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