静脉全身麻醉药对大鼠皮质突触体[3H]γ-氨基丁酸释放的影响。

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

作者信息

Murugaiah K D, Hemmings H C

机构信息

Department of Anesthesiology, Cornell University Medical College, New York, New York 10021, USA.

出版信息

Anesthesiology. 1998 Oct;89(4):919-28. doi: 10.1097/00000542-199810000-00017.

DOI:10.1097/00000542-199810000-00017

PMID:9778010

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.

摘要

背景

全身麻醉药增强中枢神经系统中γ-氨基丁酸（GABA）介导的抑制性传递，这归因于GABA A受体介导的突触后效应。然而，突触前机制在全身麻醉作用中的作用尚未得到充分表征，并且关于麻醉药对GABA释放影响的证据存在争议。研究了几种静脉全身麻醉药对大鼠脑皮质突触体（分离的神经末梢）中[3H]GABA释放的影响。

方法

用[3H]GABA预加载纯化的突触体，并用含有氨氧基乙酸和哌啶酸的缓冲液进行灌流，分别抑制GABA代谢和再摄取。在不存在或存在各种麻醉药、细胞外Ca2+、GABA受体激动剂和拮抗剂以及2,4-二氨基丁酸的情况下，评估灌流液中自发的和氯化钾去极化升高诱发的[3H]GABA释放。

结果

丙泊酚、依托咪酯、戊巴比妥和alphaxalone（但不是氯胺酮）以浓度依赖性方式增强氯化钾诱发的[3H]GABA释放（增强1.3至2.9倍），半数有效浓度值分别为5.4±2.8微摩尔（平均值±标准误）、10.1±2.1微摩尔、18.8±5.8微摩尔和4.4±2.0微摩尔。丙泊酚还使自发的[3H]GABA释放增加了1.7倍（半数有效浓度=7.1±3.4微摩尔）。丙泊酚对[3H]GABA释放的促进作用依赖于Ca2+，并被荷包牡丹碱和印防己毒素抑制，但对用2,4-二氨基丁酸预处理不敏感，后者可耗尽细胞质GABA池。