The effect of lithium on noradrenaline-induced cyclic AMP accumulation in rat brain: Inhibition after chronic treatment and absence of supersensitivity

R. P. Ebstein, M. Hermoni, R. H. Belmaker

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

Lithium (Li) has been reported to inhibit numerous adenylate cyclases, but often these reports used clinically toxic concentrations of Li and their relevance to a theory of Li action was questionable. The present report demonstrated Li inhibition beginning at 2mM of the norepinephrine (NE)-induced cyclic AMP accumulation in a resuspended P2 pellet containing intact synaptosomes and in slices from rat cortex. The inhibition is demonstrable with isoproterenol as well and in the presence of a phosphodiesterase inhibitor. In cortical slices removed from rats treated for 21 days with therapeutically equivalent Li serum levels, NE-induced cyclic AMP accumulation is inhibited by over 70%. After cessation of 21 or 42 days of Li treatment, an enhancement of cyclic AMP accumulation to NE is not demonstrable. Rubidium and cesium do not inhibit NE-induced cyclic AMP accumulation. These ions cause an increase in basal cyclic AMP accumulation in the absence of NE, as does Li to a lesser degree. The effect of Li to inhibit NE-induced cyclic AMP accumulation is therefore specific to the Li ion, occurs at therapeutically equivalent concentrations, continues after chronic treatment and does not cause a compensatory supersensitivity in the manner of the NE-receptor blocking drugs.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume213
Issue number1
StatePublished - 1 Jan 1980
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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