title: Inhalation anaesthetic competition at high-affinity cocaine binding sites in rat brain synaptosomes.
abstract: We have shown previously that inhalation anaesthetics inhibit dopamine transport in rat synaptosomes. In order to determine if this inhibition is associated with occupancy of the cocaine site, we examined binding of [3H] (2 beta-carbomethoxy-3 beta-(4-fluorophenyl)-tropane) (3H-CFT) in the presence of halothane or isoflurane 0.01-5 mmol litre-1 in rat brain synaptosomes. Both anaesthetics inhibited 3H-CFT binding (mean Ki 0.61 (SEM 0.12) and 0.75 (0.21) mmol litre-1, respectively), by increasing Kd (13.8 (0.6) and 29.8 (12.8) nmol litre-1, respectively) compared with control (8.02 (0.5) nmol litre-1) (P < 0.01). Halothane did not change Bmax, but isoflurane increased it significantly. Cocaine protected CFT sites from N-ethylmaleimide alkylation, but neither anaesthetic did. Photoaffinity labelling with halothane significantly inhibited 3H-CFT binding compared with UV-exposed controls. We conclude that clinically relevant concentrations of both anaesthetics inhibit high-affinity CFT binding, and the data suggest overlapping sites for halothane and CFT.
authors.affiliation: Department of Anesthesia and Physiology, University of Pennsylvania Medical Center, Philadelphia 19104-4283.
authors.forename: R G
authors.initials: RG
authors.lastname: Eckenhoff
authors.forename: D
authors.initials: D
authors.lastname: Fagan
mesh_terms: D000769:Anesthesia, Inhalation; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D007530:Isoflurane; D003042:Cocaine; D006221:Halothane