THE RELATIONSHIP BETWEEN NERVE TERMINAL ADENOSINE TRIPHOSPHATASES AND NEUROTRANSMITTER RELEASE: AS DETERMINED BY THE USE OF ANTIDEPRESSANT AND OTHER CNS‐ACTIVE DRUGS

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Abstract
1 The role of adenosine triphosphatases (ATPases) in neurotransmitter release was studied using nerve terminals (synaptosomes) prepared from rat cerebral cortex as a model. 2 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. 3 At low concentrations of antidepressants (10−8 and 10−7 m) release of NA was enhanced but there was no effect on ACh release. 4 Other drugs which inhibit Na+, K+-ATPase increased basal NA release as did drugs which inhibited vesicular Mg2+-ATPase. 5 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.