Griffiths R, Greiff J M, Boyle E, Rowbotham D J, Norman R I
Department of Anaesthesia, University of Leicester, Royal Infirmary, United Kingdom.
Anesthesiology. 1994 Oct;81(4):953-8. doi: 10.1097/00000542-199410000-00022.
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.
[Methyl-3H]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-3H]choline uptake was studied.
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-3H]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%.
Noncompetitive inhibition of [methyl-3H]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.
乙酰胆碱是一种与意识维持相关的兴奋性神经递质。胆碱摄取是乙酰胆碱合成中的限速步骤，可能是挥发性麻醉剂作用的靶点。
使用大鼠皮质突触体研究[甲基 - 3H]胆碱摄取。将制剂暴露于空气中作为对照，或暴露于等效分压（2.4大鼠MAC）的恩氟烷、氟烷或异氟烷中。此外，研究了氟烷对[甲基 - 3H]胆碱摄取的剂量 - 反应关系。
在恩氟烷（5.5%，2.4大鼠MAC）和异氟烷（3.5%，2.4大鼠MAC）存在下，最大摄取速率显著降低24%，在氟烷（3%，2.4大鼠MAC）存在下降低38%，且每种药物存在时米氏常数无变化。观察到在氟烷浓度高达3%时，[甲基 - 3H]胆碱摄取抑制与氟烷浓度之间呈线性关系，高于此浓度则无进一步抑制。导致总胆碱摄取半数抑制的氟烷浓度为1.5%。
在体外突触体制备中已证实挥发性麻醉剂对[甲基 - 3H]胆碱摄取有非竞争性抑制作用。如果在体内存在，麻醉敏感性胆碱摄取的降低可能会减少乙酰胆碱的突触前可用性，从而有助于麻醉过程。
