Propofol-induced anesthesia in mice is mediated by γ-aminobutyric acid-A and excitatory amino acid receptors
Propofol-induced anesthesia in mice is mediated by γ-aminobutyric acid-A and excitatory amino acid receptors
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DOI：
10.1213/01.ane.0000059742.62646.40
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发表时间：
2003-08-01
影响因子：
5.7
通讯作者：
Kawahara, M
中科院分区：
文献类型：
--
作者：
Irifune, M;Takarada, T;Kawahara, M
为了阐明γ-氨基丁酸(GABA)(A)受体复合体和兴奋性氨基酸受体(N-甲基-D-天冬氨酸[NMDA]和非NMDA受体)在异丙酚诱导麻醉中的作用，我们观察了GABA能和谷氨酸能药对异丙酚麻醉的行为学影响。所有药物均经腹膜腔给药。采用翻正反射试验评价全身麻醉药的效力。GABA(A)受体激动剂Muscimol增强异丙酚(140 mg/kg；翻正反射消失50%有效剂量)诱导的麻醉。同样，苯二氮卓类受体激动剂安定和NMDA受体拮抗剂NM-801增加了异丙酚的麻醉，但非NNMA受体拮抗剂CNQX不能。GABAA受体拮抗剂荷包牡丹碱可拮抗异丙酚(200 mg/kg；翻正反射消失95%有效剂量)诱导的麻醉。然而，苯二氮卓类受体拮抗剂氟马西尼、γ-氨基丁酸合成抑制剂L-烯丙基甘氨酸和N-甲基-D-天冬氨酸受体激动剂均不能逆转异丙酚的麻醉。相反，非NMDA受体激动剂海人酸能增强异丙酚的麻醉。这些结果表明，异丙酚诱导的麻醉至少部分是由GABA(A)和兴奋性氨基酸受体介导的。
To elucidate the role of gamma-aminobutyric acid (GABA)(A) receptor complex and excitatory amino acid receptors (N-methyl-D-aspartate [NMDA] and non-NMDA receptors) in propofol-induced anesthesia, we examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol anesthesia in mice. All drugs were administered intraperitoneally. General anesthetic potencies were evaluated using a righting reflex assay. The GABA(A) receptor agonist muscimol potentiated propofol (140 mg/kg; 50% effective dose for loss of righting reflex) induced anesthesia. Similarly, the benzodiazepine receptor agonist diazepam and the NMDA receptor antagonist NM-801 augmented propofol anesthesia, but the non-NNMA receptor antagonist CNQX did not. In contrast, the GABAA receptor antagonist bicuculline antagonized propofol (200 mg/kg; 95% effective dose for loss of righting reflex) induced anesthesia. However, neither the benzodiazepine receptor antagonist flumazenil, the GABA synthesis inhibitor L-allylglycine, nor the NMDA receptor agonist NMDA reversed propofol anesthesia. Conversely, the non-NMDA receptor agonist kainate enhanced propofol anesthesia. These results suggest that propofol-induced anesthesia is mediated, at least in part, by both GABA(A) and excitatory amino acid receptors.