VOLATILE ANESTHETIC AGENTS INHIBIT CHOLINE UPTAKE INTO RAT SYNAPTOSOMES

Background: Acetylcholine is an excitatory neurotransmitter associated with the maintenance of consciousness. Choline uptake is the rate-limiting step in acetylcholine synthesis and may be a target for the action of volatile anesthetic agents. Methods: [Methyl-H-3]choline uptake was investigated using rat cortical synaptosomes. The preparation was exposed to air, as control, or equipotent partial pressures (2.4 rat MAC) of enflurane, halothane or isoflurane. In addition, the dose-response relation for halothane on [methyl-H-3]choline uptake was studied. Results: The maximum rate of uptake was reduced significantly by 24% in the presence of enflurane (5.5%, 2.4 rat MAC) and isoflurane (3.5%, 2.4 rat MAC) and by 38% in the presence of halothane (3%, 2.4 rat MAC) with no change in Michaelis constant in the presence of each agent. A linear relation between the inhibition of [methyl-H-3]choline uptake and the concentration of halothane was observed up to 3% halothane above which there was no further inhibition. The concentration of halothane resulting in half-maximum inhibition of total choline uptake was 1.5%. Conclusions: Noncompetitive inhibition of [methyl-H-3]choline uptake by volatile anesthetic agents has been demonstrated in the in vitro synaptosome preparation. If present in vivo reduction in anesthetic-sensitive choline uptake may reduce the presynaptic availability of acetylcholine and hence contribute to the process of anesthesia.