PMID: 2493069Mar 1, 1989Paper

Compared effects of two vesicular acetylcholine uptake blockers, AH5183 and cetiedil, on cholinergic functions in Torpedo synaptosomes: acetylcholine synthesis, choline transport, vesicular uptake, and evoked acetylcholine release

Journal of Neurochemistry
Y M Gaudry-TalarmainS O'Regan

Abstract

We examined the effects of two drugs, AH5183 and cetiedil, demonstrated to be potent inhibitors of acetylcholine (ACh) transport by isolated synaptic vesicles on cholinergic functions in Torpedo synaptosomes. AH5183 exhibited a high specificity toward vesicular ACh transport, whereas cetiedil was shown to inhibit both high-affinity choline uptake and vesicular ACh transport. Choline acetyltransferase was not affected by either drug. High external choline concentrations permitted us to overcome cetiedil inhibition of high-affinity choline transport, and thus synthesis of [14C]ACh in treated preparations was similar to that in controls. We then tested evoked ACh release in drug-treated synaptosomes under conditions where ACh translocation into the vesicles was blocked. We observed that ACh release was impaired only in cetiedil-treated preparations; synaptosomes treated with AH5183 behaved like the controls. Thus, this comparative study on isolated nerve endings allowed us to dissociate two steps in drug action: upstream, where both AH5183 and cetiedil are efficient blockers of the vesicular ACh translocation, and downstream, where only cetiedil is able to block the ACh release process.

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Citations

Apr 11, 2000·Microscopy Research and Technique·N Morel, M Israël
Aug 3, 1989·European Journal of Pharmacology·Y M Gaudry-TalarmainM Israël
Mar 19, 1991·European Journal of Pharmacology·R GirodY Dunant
Jul 9, 1991·European Journal of Pharmacology·P AasF Fonnum
Dec 25, 2010·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Hanaa H Ahmed
May 11, 1992·Annals of the New York Academy of Sciences·I Hanin

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