Intracellular lithium and cyclic AMP levels are mutually regulated in neuronal cells

L. P. Montezinho, C. B. Duarte, C. P. Fonseca, Y. Glinka, B. Layden, D. Mota De Freitas, C. F G C Geraldes, M. M C A Castro

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


In this work, we studied the effect of intracellular 3′,5′- cyclic adenosine monophosphate (cAMP) on Li+ transport in SH-SY5Y cells. The cells were stimulated with forskolin, an adenylate cyclase activator, or with the cAMP analogue, dibutyryl-cAMP. It was observed that under forskolin stimulation both the Li+ influx rate constant and the Li+ accumulation in these cells were increased. Dibutyryl-cAMP also increased Li+ uptake and identical results were obtained with cortical and hippocampal neurons. The inhibitor of the Na+/Ca2+ exchanger, KB-R7943, reduced the influx of Li+ under resting conditions, and completely inhibited the effect of forskolin on the accumulation of the cation. Intracellular Ca2+ chelation, or inhibition of N-type voltage-sensitive Ca2+ channels, or inhibition of cAMP-dependent protein kinase (PKA) also abolished the effect of forskolin on Li+ uptake. The involvement of Ca2+ on forskolin-induced Li+ uptake was confirmed by intracellular free Ca2+ measurements using fluorescence spectroscopy. Exposure of SH-SY5Y cells to 1 mM Li+ for 24 h increased basal cAMP levels, but preincubation with Li+, at the same concentration, decreased cAMP production in response to forskolin. To summarize, these results demonstrate that intracellular cAMP levels regulate the uptake of Li+ in a Ca2+-dependent manner, and indicate that Li+ plays an important role in the homeostasis of this second messenger in neuronal cells.

Original languageEnglish (US)
Pages (from-to)920-930
Number of pages11
JournalJournal of neurochemistry
Issue number4
StatePublished - Aug 2004


  • Calcium
  • Forskolin
  • Lithium
  • Na/Ca exchanger
  • cAMP

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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