Abstract
Effect of denbufylline, a low Km phosphodiesterase inhibitor, on cerebral cholinergic neurons was investigated using male Wistar rats. Single administrations of denbufylline (3, 10 and 30 mg/kg, p.o.) decreased cerebral cortical, hippocampal and striatal acetylcholine (ACh) contents in a dose-dependent manner. However, denbufylline (30 mg/kg, p.o.) had no effect on the activities of ACh synthesizing and degrading enzymes in these brain areas. In vitro addition of denbufylline (10-8 - 10-4M) produced no significant change in [3H]choline uptake in striatal slices, while denbufylline (10-4M) increased high (20 mM) potassium-evoked endogenous ACh release from striatal slices. Denbufylline (30 mg/kg, p.o.) increased cyclic AMP (cAMP) contents in the cerebral cortex, hippocampus and striatum. In vitro addition of dibutyryl cAMP (5 × 10-3M) also accentuated the high (20 mM) potassiumevoked endogenous ACh release from striatal slices. These results suggest that denbufylline may induce the facilitation of ACh turnover by enhancing endogenous ACh release via the increase of cAMP content in the brain.
