The relationship between nerve terminal adenosine triphosphatases and neurotransmitter release: as determined by the use of antidepressant and other CNS-active drugs.
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 increase 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.
D000109:Acetylcholine / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism*
D000927:Anticonvulsants; D000928:Antidepressive Agents; D018377:Neurotransmitter Agents; D010042:Ouabain; D010672:Phenytoin; D000251:Adenosine Triphosphatases; D000109:Acetylcholine; D009638:Norepinephrine