Effects of enflurane on 5-hydroxytryptamine transport in synaptosomes from rat brain.
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 resulted in a concentration-dependent inhibition of serotonin uptake; the apparent I50 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 KI 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.
Martin
D C
DC
Department of Anesthesiology, Medical College of Georgia, Augusta 30912-2700.
Adams
R J
RJ
Aronstam
R S
RS
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004737:Enflurane / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D012701:Serotonin; D004737:Enflurane; D012964:Sodium