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

• Published in: Journal of neurochemistry 2004-08, Vol.90 (4), p.920-930
• Main Authors: Montezinho, L. P., B. Duarte, C., Fonseca, C. P., Glinka, Y., Layden, B., Mota de Freitas, D., Geraldes, C. F. G. C., Castro, M. M. C. A.
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - drug effects; Adenylyl Cyclases - metabolism; Animals; Biological and medical sciences; Bucladesine - pharmacology; calcium; Calcium - metabolism; cAMP; Cells, Cultured; Colforsin - pharmacology; Cyclic AMP - metabolism; forskolin; Humans; Intracellular Fluid - metabolism; Ion Transport - drug effects; lithium; Lithium - metabolism; Lithium - pharmacokinetics; Lithium - pharmacology; Medical sciences; Na+/Ca2+ exchanger; Neuroblastoma; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2004.02551.x

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.