Valproic acid differs in its in vitro effect on glutamic acid decarboxylase activity in neonatal and adult rat brain.
1. The in vitro effect of valproic acid (VA) (10(-6) to 10(-3) M) on glutamic acid decarboxylase (GAD) activity in whole brain and cerebral cortex (CC) of neonates and of adult rats was examined. 2. VA did not induce changes on GAD activity either in CC or in the rest of the brain (RB) of adult animals. 3. But at 10(-3) M, VA induced an increase in GAD activity in homogenates of noncortical brain areas of neonates; no increments were found in CC of these animals. This latter increase was detected in the membrane-bound fraction of the enzyme and was not due to physicochemical nonspecific changes related to the potential solvent activity of VA at this high concentration. 4. We may conclude that VA induces changes on GAD activity in neonatal stages of development but not in adult brain. Therefore, although a direct enhancement of GAD activity may play a role in the mechanism of action of VA in pediatric patients, this cannot be verified in the adult population.
Wikinski
S I
SI
Instituto de Investigaciones Farmacológicas (ININFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Acosta
G B
GB
Rubio
M C
MC
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000201:enzymology* / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014635:Valproic Acid; D005968:Glutamate Decarboxylase