Compensatory increase in synaptosomal aldehyde reductase activity in rat brain after chronic barbital treatment

The changes in brain aldehyde reductase (AIR) activities during long-term treatment of rats with barbital were studied. NADH-linked AIR activity in the synaptosomal fraction increased rapidly, and supernatant AIR activity rose later during barbital treatment. With respect to NADPH-linked AIR, two distinct K m values were observed for p-nitrobenzaldehyde. The low- K m enzyme had a higher K i value than the high- K m enzyme. Although the elevation of NADPH-linked AIR activity under the routine assay conditions was less remarkable, V max values of the low- K m enzyme were greatly increased in both the synaptosomal and the supernatant fractions by chronic barbital treatment. In addition, the K i value of low- K m AIR in synaptosomes was greater in barbital-treated animals than in control animals. K m values were unchanged in either fraction by chronic barbital treatment. These data suggest that chronic barbital treatment resulted in a compensatory increase in the activity of AIR with low K m , which is less sensitive to barbital and utilizes either NADH or NADPH, in synaptosomes.