Effects of intravenous general anesthetics on [3H]GABA release from rat cortical synaptosomes.

Abstract:

BACKGROUND:Potentiation by general anesthetics of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission in the central nervous system is attributed to GABA(A) receptor-mediated postsynaptic effects. However, the role of presynaptic mechanisms in general anesthetic action is not well characterized, and evidence for anesthetic effects on GABA release is controversial. The effects of several intravenous general anesthetics on [3H]GABA release from rat cerebrocortical synaptosomes (isolated nerve terminals) were investigated. METHODS:Purified synaptosomes were preloaded with [3H]GABA and superfused with buffer containing aminooxyacetic acid and nipecotic acid to inhibit GABA metabolism and reuptake, respectively. Spontaneous and elevated potassium chloride depolarization-evoked [3H]GABA release were evaluated in the superfusate in the absence or presence of various anesthetics, extracellular Ca2+, GABA receptor agonists and antagonists, and 2,4-diaminobutyric acid. RESULTS:Propofol, etomidate, pentobarbital, and alphaxalone, but not ketamine, potentiated potassium chloride-evoked [3H]GABA release (by 1.3 to 2.9 times) in a concentration-dependent manner, with median effective concentration values of 5.4 +/- 2.8 microM (mean +/- SEM), 10.1 +/- 2.1 microM, 18.8 +/- 5.8 microM, and 4.4 +/- 2.0 microM. Propofol also increased spontaneous [3H]GABA release by 1.7 times (median effective concentration = 7.1 +/- 3.4 microM). Propofol facilitation of [3H]GABA release was Ca2+ dependent and inhibited by bicuculline and picrotoxin, but was insensitive to pretreatment with 2,4-diaminobutyric acid, which depletes cytoplasmic GABA pools. CONCLUSIONS:Low concentrations of propofol, etomidate, pentobarbital, and alphaxalone facilitated [3H]GABA release from cortical nerve terminals. General anesthetics may facilitate inhibitory GABA-ergic synaptic transmission by a presynaptic mechanism in addition to their well-known postsynaptic actions.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Murugaiah KD,Hemmings HC Jr

doi

10.1097/00000542-199810000-00017

subject

Has Abstract

pub_date

1998-10-01 00:00:00

pages

919-28

issue

4

eissn

0003-3022

issn

1528-1175

journal_volume

89

pub_type

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