The anesthetic mechanism of urethane: The effects on rotransmitter-gated ion channels
The anesthetic mechanism of urethane: The effects on rotransmitter-gated ion channels
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DOI：
10.1097/00000539-200202000-00015
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发表时间：
2002-02-01
影响因子：
5.7
通讯作者：
Harris, RA
中科院分区：
文献类型：
--
作者：
Hara, K;Harris, RA
乌拉坦被广泛用作动物研究的麻醉剂，因为它对心血管和呼吸系统以及维持脊髓反射的影响最小。尽管它在动物研究中很有用，但关于它的分子作用还没有报道。我们设计这项研究是为了确定乌拉坦是否影响神经递质门控离子通道。我们研究了乌拉坦对非洲爪哇卵母细胞表达重组γ-氨基丁酸(A)、甘氨酸、N-甲基-D-天冬氨酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸和神经元型烟碱型乙酰胆碱受体的影响。乌拉坦增强神经元烟碱型乙酰胆碱、γ-氨基丁酸(A)和甘氨酸受体的功能，对N-甲基-D-天冬氨酸和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体的抑制作用呈浓度依赖性。在接近麻醉剂有效浓度50%的浓度下，氨基甲酸乙酯对所有被测试的通道都有轻微的影响，这表明其作用缺乏单一的主要靶点。这可能解释了它作为兽医麻醉剂的用处。然而，较大浓度的氨基甲酸酯对所有通道都有显著影响。这些发现不仅对麻醉药的分子机制有了深入的了解，而且还警告说，乌拉坦对多个神经递质系统的影响可能会使乌拉坦麻醉动物的神经生理学测量变得复杂。我们的结果还表明，多个感受器系统的微小变化可以产生麻醉。
Urethane is widely used as an anesthetic for animal studies because of its minimal effects on cardiovascular and respiratory systems and maintenance of spinal reflexes. Despite its usefulness in animal research, there are no reports concerning its molecular actions. We designed this study to determine whether urethane affects neurotransmitter-gated ion channels. We examined the effects of urethane on recombinant gamma-aminobutyric acid(A), glycine, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. Urethane potentiated the functions of neuronal nicotinic acetylcholine, gamma-aminobutyric acid(A), and glycine receptors, and it inhibited N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in a concentration-dependent manner. At concentrations close to anesthetic 50% effective concentration, urethane had modest effects on all channels tested, suggesting the lack of a single predominant target for its action. This may account for its usefulness as a veterinary anesthetic. However, a large concentration of urethane exerts marked effects on all channels. These findings not only give insight into the molecular mechanism of anesthetics but also caution that neurophysiologic measurements from animals anesthetized with urethane may be complicated by the effects of urethane on multiple neurotransmitter systems. Our results also suggest that small changes in multiple receptor systems can produce anesthesia.