Abstract
The administration of volatile anesthetics to laboratory animals has been reported to alter brain 5-hydroxytryptamine (serotonin, 5-HT) homeostasis. To examine a potential anesthetic action that could account for these observations, the effect of enflurane on 5-HT accumulation by rat brain synaptosomes was examined. Established techniques were used to prepare synaptosomes and perform uptake assays using [ 3H]5-hydroxytryptamine as substrate. Exposure of the synaptosomes to enflurane 0resulted in a concentration-dependent inhibition of serotonin uptake; the apparent I 50 was 1.4 ± 0.3 mM enflurane. Maximum inhibition was observed between enflurane concentrations of 2.6 and 4.3 mM, which inhibited uptake between 62 and 70%. The inhibition was rapid and reversible, and kinetic analysis of the inhibition was consistent with competitive inhibition by enflurane of 5-HT uptake with an apparent K 1 of 1.61 ± 0.07 mM. In summary, exposure of synaptosomes to clinically relevant concentrations of enflurane resulted in a rapid, concentration-dependent, and reversible inhibition of 5-HT accumulation. These observations could represent a molecular interaction contributing to the anesthetic properties of enflurane and other volatile anesthetics.
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