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Reversible and Irreversible Inhibition of High‐Affinity Choline Transport Caused by Ethylcholine Aziridinium Ion
Author(s) -
Pittel Zipora,
Fisher Abraham,
Heldman Eliahu
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb02888.x
Subject(s) - choline , chemistry , extracellular , cholinergic , in vivo , kinetics , ic50 , biophysics , in vitro , hippocampal formation , transporter , biochemistry , pharmacology , endocrinology , biology , physics , microbiology and biotechnology , quantum mechanics , gene
The effect of ethylcholine aziridinium ion (AF64A) on choline transport in hippocampal, striatal, and cerebrocortical synaptosomes was studied. Synaptosomes prepared from these three brain regions were equally sensitive to AF64A. Low concentrations of AF64A produced a reversible inhibition (IC 50 values = 1.35–2.25 μ M ), whereas higher concentrations produced an irreversible inhibition (IC 50 values = 25–30 μ M ), which started as competitive. The irreversible component of the inhibition was independent of extracellular Na + concentration, a finding suggesting that the choline transporter is alkylated at its outward position. The kinetics of the inhibition were rapid and similar in the three brain regions examined. The high‐affinity choline transport was more sensitive to the toxin than the low‐affinity choline transport. Based on these results, we propose a kinetic model that explains the reversible and the irreversible inhibitions induced by AF64A. The possible relationships between the concentrations that in vitro produce reversible and irreversible inhibition and those that in vivo produce selective and nonselective cholinergic hypofunc‐tion are discussed.