Abstract
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 language | English (US) |
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Pages (from-to) | 920-930 |
Number of pages | 11 |
Journal | Journal of neurochemistry |
Volume | 90 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2004 |
Keywords
- Calcium
- Forskolin
- Lithium
- Na/Ca exchanger
- cAMP
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience