title: Enhanced choline acetyltransferase activity does not explain the action of inhaled convulsants.
abstract: Enhancement of choline acetyltransferase (ChAT) activity and increased intraneuronal acetylcholine (ACh) may explain the convulsant activity of some inhaled compounds. Enflurane, for example, enhances such activity. Accordingly, we measured choline acetyltransferase (ChAT) activity in rat cortical synaptosomes in the presence of two inhaled convulsants, flurothyl (CF3CH2OCH2CF3) and 1,2-dichlorohexafluorocyclobutane at partial pressures below and greatly exceeding those which produce convulsions in vivo. Neither agent changed the kinetic parameters, maximum velocity (vmax) or Michaelis constant (Km). The vmax for controls in the flurothyl series was 016 (0.06) nmol mg-1 min-1 and the Km was 0.23 (0.11) mmol litre-1. For the 1,2-dichlorohexafluorocyclobutane series of experiments the results for the controls were vmax 0.23 (0.10) nmol mg-1 min-1 and Km 0.20 (0.08) mmol litre-1. Modification of ChAT activity did not contribute to the excitatory effects of these agents.
authors.affiliation: University Department of Anaesthesia, Leicester Royal Infirmary.
authors.forename: R
authors.initials: R
authors.lastname: Griffiths
authors.forename: P
authors.initials: P
authors.lastname: Ionescu
authors.forename: Z
authors.initials: Z
authors.lastname: Fang
authors.forename: D D
authors.initials: DD
authors.lastname: Koblin
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
mesh_terms: D000280:Administration, Inhalation; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D017402:Chlorofluorocarbons / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000187:drug effects* / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D003503:Cyclobutanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005481:Flurothyl / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
chemical_list: D000777:Anesthetics; D017402:Chlorofluorocarbons; D003292:Convulsants; D003503:Cyclobutanes; C090640:1,2-dichloro-1,2,3,3,4,4-hexafluorocyclobutane; D005481:Flurothyl; D002795:Choline O-Acetyltransferase