Tetrahydroaminoacridine (tacrine) stimulates neurosecretion at mammalian motor endplates.
1. Tacrine (20 microM) induced, like 4-aminoquinoline (4-AQ, 200 microM), the appearance of a population of miniature endplate potentials (m.e.p.ps) with more than twice the normal amplitude or time-to-peak. The times-to-peak of nerve impulse-evoked endplate potentials were not similarly affected. 2. Cholinesterase inhibition by edrophonium (25 microM) did not prevent tacrine or 4-AQ from inducing this population of m.e.p.ps. 3. Nerve-muscle preparations in which the normal calcium-sensitive quantal release of acetylcholine had been blocked by botulinum neurotoxin type A also responded to tacrine by an increase in the frequency of giant or slow m.e.p.ps. 4. Reduction of the temperature from 30 degrees to 14 degrees C reduced the frequency of giant or slow m.e.p.ps induced either by tacrine or by 4-AQ. A similar effect was obtained by colchicine (5 mM). This supports the idea that proximo-distal axonal transport is required for the secretory activity. 5. The neurosecretion evoked by tacrine could explain the therapeutic effects of the drug claimed in the treatment of Alzheimer's type of dementia.
Thesleff
S
S
Department of Pharmacology, University of Lund, Sweden.
Sellin
L C
LC
Tågerud
S
S
D000109:Acetylcholine / Q000378:metabolism; D000609:Aminoacridines / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D004491:Edrophonium / Q000494:pharmacology; D004594:Electrophysiology; D005089:Exocytosis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D010791:Phrenic Nerve / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D013619:Tacrine / Q000494:pharmacology*; D013696:Temperature
D000609:Aminoacridines; D000634:Aminoquinolines; D013619:Tacrine; D004491:Edrophonium; D001905:Botulinum Toxins; C001920:4-aminoquinoline; D000109:Acetylcholine