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-lim iting step in acetylcholine synthesis and may be a target for the acti on 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 M AC) of enflurane, halothane or isoflurane. In addition, the dose-respo nse relation for halothane on [methyl-H-3]choline uptake was studied. Results: The maximum rate of uptake was reduced significantly by 24% i n 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 abo ve which there was no further inhibition. The concentration of halotha ne resulting in half-maximum inhibition of total choline uptake was 1. 5%. Conclusions: Noncompetitive inhibition of [methyl-H-3]choline upta ke by volatile anesthetic agents has been demonstrated in the in vitro synaptosome preparation. If present in vivo reduction in anesthetic-s ensitive choline uptake may reduce the presynaptic availability of ace tylcholine and hence contribute to the process of anesthesia.