Tacrine-induced increase in the release of spontaneous high quantal content events in Torpedo electric organ.
1. The anticholinesterases, tacrine (100 microM) and physostigmine (60 microM) had different effects on the amplitude distribution and kinetics of miniature endplate currents (m.e.p.cs) recorded extracellularly from the electric organ of Torpedo marmorata. 2. Tacrine increased the ratio of giant miniatures (larger than 4 mV of amplitude) to more than 20% of recorded spontaneous events. In the presence of physostigmine such events represented only 4%. 3. Both tacrine and physostigmine increased the rise time and the decay phase of normal-sized m.e.p.cs when compared to control conditions. Both effects were significantly greater for tacrine. 4. We have tested the specificity of the tacrine effect on ectoenzyme activities associated with plasma membranes of these pure cholinergic nerve endings. Tacrine does not act unspecifically on every ectoenzyme, because it is not able to block the ectoapyrase activity even at a concentration 100 fold greater than that required to inhibit 94% of AChE. 5. We conclude that the differential effects of tacrine and physostigmine can be explained in terms of undetermined presynaptic actions of tacrine, while comparable effects of the two compounds can be explained through a shared anticholinesterase activity.
Departament de Biologia Cel.lular i Anatomia Patológica, Facultat de Medicina, Hospital de Bellvitge, Universitat de Barcelona, Spain.
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Cantí
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Martí
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Marsal
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Solsona
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004557:Electric Organ / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009045:Motor Endplate / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000201:enzymology; D010830:Physostigmine / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013619:Tacrine / Q000494:pharmacology*; D014101:Torpedo / Q000502:physiology*
D002800:Cholinesterase Inhibitors; D013619:Tacrine; D010830:Physostigmine; D000109:Acetylcholine