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A novel target of lithium therapy
Author(s) -
Yenush Lynne,
Bellés José M.,
López-Coronado José M.,
Gil-Mascarell Rosario,
Serrano Ramón,
Rodrı́guez Pedro L.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01183-2
Subject(s) - lithium therapy , lithium (medication) , chemistry , medicine , bipolar disorder
Phosphatases converting 3′‐phosphoadenosine 5′‐phosphate (PAP) into adenosine 5′‐phosphate are of fundamental importance in living cells as the accumulation of PAP is toxic to several cellular systems. These enzymes are lithium‐sensitive and we have characterized a human PAP phosphatase as a potential target of lithium therapy. A cDNA encoding a human enzyme was identified by data base screening, expressed in Escherichia coli and the 33 kDa protein purified to homogeneity. The enzyme exhibits high affinity for PAP ( K m <1 μM) and is sensitive to subtherapeutic concentrations of lithium (IC 50 =0.3 mM). The human enzyme also hydrolyzes inositol‐1,4‐bisphosphate with high affinity ( K m =0.4 μM), therefore it can be considered as a dual specificity enzyme with high affinity (μM range) for both PAP and inositol‐1,4‐bisphosphate. Hydrolysis of inositol‐1,4‐bisphosphate was also inhibited by lithium (IC 50 =0.6 mM). Thus, we present experimental evidence for a novel target of lithium therapy, which could explain some of the side effects of this therapy.