TY - JOUR
T1 - Valproyl-CoA and esterified valproic acid are not found in brains of rats treated with valproic acid, but the brain concentrations of CoA and acetyl-CoA are altered
AU - Deutsch, Joseph
AU - Rapoport, Stanley I.
AU - Rosenberger, Thad A.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Sodium valproate and lithium are used to treat bipolar disorder. In rats, both reduce the turnover of arachidonic acid in several brain phospholipids, suggesting that arachidonate turnover is a common target of action of these mood stabilizers. However, the mechanisms by which these drugs reduce arachidonate turnover in brain are not the same. Lithium decreases turnover by reducing the activity and expression of the 85-kDa type IVA cytosolic phospholipase A2 (cPLA2); valproate does not affect cPLA2 activity or expression. To test whether valproate alters neural membrane order by direct esterification into phospholipid or by interrupting intermediary CoA metabolism, we measured valproyl-CoA, esterified valproate, and short chain acyl-CoAs in brains from control rats and rats treated chronically with sodium valproate. Valproyl-CoA and esterified forms of valproate were not found in brain with detection limits of 25 and 37.5 pmol/g brain-1, respectively. Valproate treatment did result in a 1.4-fold decrease and 1.5-fold increase in the brain concentrations of free CoA and acetyl-CoA when compared to control. Therefore the reduction of brain arachidonic acid turnover by chronic valproate in rats is not related to the formation of valproyl-CoA or esterified valproate, but may involve changes in the intermediary metabolism of CoA and short chain acyl-CoA.
AB - Sodium valproate and lithium are used to treat bipolar disorder. In rats, both reduce the turnover of arachidonic acid in several brain phospholipids, suggesting that arachidonate turnover is a common target of action of these mood stabilizers. However, the mechanisms by which these drugs reduce arachidonate turnover in brain are not the same. Lithium decreases turnover by reducing the activity and expression of the 85-kDa type IVA cytosolic phospholipase A2 (cPLA2); valproate does not affect cPLA2 activity or expression. To test whether valproate alters neural membrane order by direct esterification into phospholipid or by interrupting intermediary CoA metabolism, we measured valproyl-CoA, esterified valproate, and short chain acyl-CoAs in brains from control rats and rats treated chronically with sodium valproate. Valproyl-CoA and esterified forms of valproate were not found in brain with detection limits of 25 and 37.5 pmol/g brain-1, respectively. Valproate treatment did result in a 1.4-fold decrease and 1.5-fold increase in the brain concentrations of free CoA and acetyl-CoA when compared to control. Therefore the reduction of brain arachidonic acid turnover by chronic valproate in rats is not related to the formation of valproyl-CoA or esterified valproate, but may involve changes in the intermediary metabolism of CoA and short chain acyl-CoA.
KW - Acetyl-CoA
KW - Arachidonic acid
KW - Brain
KW - Coenzyme A
KW - Fatty acid
KW - Phospholipid
KW - Valproic acid
UR - http://www.scopus.com/inward/record.url?scp=0037409740&partnerID=8YFLogxK
U2 - 10.1023/A:1023267224819
DO - 10.1023/A:1023267224819
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C2 - 12718439
AN - SCOPUS:0037409740
SN - 0364-3190
VL - 28
SP - 861
EP - 866
JO - Neurochemical Research
JF - Neurochemical Research
IS - 6
ER -