The "antidementia drug" pantoyl-gamma-aminobutyric acid increases high affinity uptake of choline by slices of rat brain.

ABSTRACT

Studies were made on the effects of an "antidementia drug", pantoyl-gamma-aminobutyric acid (pantoyl-GABA), on high affinity uptake of choline by slices of rat brain. Depolarization caused by increasing the K+ concentration to 25 mM for 30 min before incubation with [3H]choline enhanced the uptake of radioactivity by slices of cerebral cortex, hippocampus and striatum during a 5 min incubation in the presence of 1 microM [3H]choline. Pantoyl-GABA (1 mM) increased the depolarization-induced uptake of radioactivity by the slices of cortex and hippocampus, but not by the slices of striatum; it had little effect on the uptake when the slices were not depolarized. It also had no effect when the slices were depolarized in the incubation medium without Ca2+. Since the high affinity uptake of choline is considered to be a regulatory step in the synthesis of acetylcholine (ACh), these results suggest that pantoyl-GABA increases the synthesis of ACh in cholinergic terminals in the cerebral cortex and hippocampus. This action may be involved in its effect as an antidementia drug, because cholinergic deficits are assumed to occur in Alzheimer's disease.