title: Classification of the mode of inhibition of high-affinity choline uptake using capillary electrophoresis with electrochemical detection at an enzyme-modified microelectrode.
abstract: A nonradiochemical in vitro assay using capillary electrophoresis with electrochemical detection at an enzyme-modified microelectrode has been developed to evaluate the inhibition of high-affinity choline transport in synaptosomes. Quantitative analysis of high-affinity choline transporter rates as a function of inhibitor and substrate concentrations allowed determination of the mode of inhibition for the quaternary ammonium-catechol-based inhibitors 3-[(trimethylammonio)methyl]catechol, N,N-dimethylepinephrine, and 6-hydroxy-N,N-dimethylepinephrine. The results are compared to the well-characterized inhibitor of choline transport, hemicholinium-3.
authors.affiliation: Department of Chemistry, College of Arts and Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Barkhimer
authors.forename: Jon R
authors.initials: JR
authors.lastname: Kirchhoff
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hudson
authors.forename: William S
authors.initials: WS
authors.lastname: Messer
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D002794:Choline / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics*; D018678:Cholinergic Agents / Q000494:pharmacology; D004563:Electrochemistry; D019075:Electrophoresis, Capillary / Q000379:methods*; D004800:Enzymes, Immobilized; D004837:Epinephrine / Q000031:analogs & derivatives / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000032:analysis; D008839:Microelectrodes; D012680:Sensitivity and Specificity; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: C102091:6-hydroxycatecholine; D018678:Cholinergic Agents; D004800:Enzymes, Immobilized; C037919:N,N-dimethylepinephrine; D006861:Hydrogen Peroxide; D000429:Alcohol Oxidoreductases; C019888:choline oxidase; D000110:Acetylcholinesterase; D002794:Choline; D004837:Epinephrine