The relationship between nerve terminal adenosine triphosphatases and neurotransmitter release: As determined by the use of antidepressant and other CNS-active drugs

The role of adenosine triphosphatases (ATPases) in neurotransmitter release was studied using nerve terminals (synaptosomes) prepared from rat cerebral cortex as a model. Amitriptyline, nortriptyline, protriptyline, desipramine and imipramine were found to inhibit ATPases at concentrations of 10^-5 (M) and above. The drugs inhibited both the basal and electrically evoked release of acetylcholine (ACh) and noradrenaline (NA) at concentrations of 10^-4 (M) and above. At low concentrations of antidepressants (10^-8 and 10^-7 M) release of NA was enhanced but there was no affect on ACh release. Other drugs which inhibit Na⁺, K⁺-ATPase increased basal NA release as did drugs which inhibited vesicular Mg²⁺-ATPase. A model is proposed suggesting that transmitter release/re-uptake depends on (1) active Na⁺, K⁺-ATPase at the presynaptic membrane and (2) an active synaptic vesicular Mg²⁺-ATPase.