PHARMACOLOGICAL CHARACTERIZATION OF THE ACETYLCHOLINE TRANSPORT-SYSTEM IN PURIFIED TORPEDO ELECTRIC ORGAN SYNAPTIC VESICLES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 24  (1) , 48-54
Abstract
A wide variety of pharmacologically active compounds was surveyed for effects on active transport of [3H]acetylcholine by synaptic vesicles isolated from the electric organ of T. californica. In over 80 compounds tested, inhibitors of a wide range of potencies were found. The most potent inhibitor was 2-(4-phenylpiperidino)cyclohexanol (AH5183), which half-inhibited transport at 40 nM. This compound was predicted to block acetylcholine storage by vesicles in vivo. The synaptic vesicle active transport system is pharmacologically distinct from other cholinergic systems. The site of action of AH5183 and other potent inhibitors is not certain, but the possibility of trivial action on the vesicle ATPase or a vesicle proton gradient was eliminated. Vesicle exocytosis is indicated as the source of evoked acetylcholine release by nerve terminals. AH5183 appears to be the prototype for a new family of anticholinergics. The possibility that some drugs that exhibit secondary anticholinergic effects act in part by antagonizing acetylcholine storage is discussed.