TY - JOUR
T1 - Effects of enflurane on 5-hydroxytryptamine transport in synaptosomes from rat brain
AU - Martin, Dan C.
AU - Adams, Robert J.
AU - Aronstam, Robert S.
N1 - Funding Information:
We have demonstrated previously that volatile anesthetics inhibit uptake of serotonin in rat brain synaptosomes \[14\]. Inhibition of 5-HT uptake by enflurane could account for observations by previous investigators that noted changes in brain 5-HT metabolism following anesthetic administration. Accordingly, the present study characterizes the * This work was supported by a 1988 B. B. Sankey Anesthesia Advancement Award from the International Anesthesia Research Society and a Biomedical Research Support Grant from the Medical College of Georgia and was presented in part at the 1989 Meeting of the International Anesthesia Research Society. t All correspondence should be sent to: Dan C. Martin, M.D., Department of Anesthesiology, Medical College of Georgia, Augusta, GA 30912-2700.
PY - 1990/7/15
Y1 - 1990/7/15
N2 - 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 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 K1 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.
AB - 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 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 K1 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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U2 - 10.1016/0006-2952(90)90677-D
DO - 10.1016/0006-2952(90)90677-D
M3 - Article
C2 - 2375761
AN - SCOPUS:0025307462
SN - 0006-2952
VL - 40
SP - 187
EP - 192
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 2
ER -