Differences in ethanol sensitivity of brain NMDA receptors of long-sleep and short-sleep mice.
Differences in ethanol sensitivity of brain NMDA receptors of long-sleep and short-sleep mice.
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长睡眠和短睡眠小鼠脑部 NMDA 受体乙醇敏感性的差异。
DOI：
10.1111/j.1530-0277.1994.tb01454.x
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Phillips,TJ
中科院分区：
文献类型：
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作者：
Daniell,LC;Phillips,TJ
长睡眠（LS）和短睡眠（SS）小鼠，选择性繁殖的小鼠，在急性剂量乙醇产生的麻醉持续时间不同，用于确定脑NMDA受体的不同乙醇敏感性与体内乙醇麻醉作用的不同敏感性的可能关联。通过使用Ca 1的荧光指示剂Indo 1，在从两种小鼠品系的大脑皮层或大脑皮层分离的微囊（一种无细胞脑膜囊泡制备物）中测量L-谷氨酸刺激的游离细胞内钙浓度（Cal）增加，确定NMDA受体介导的反应。在没有添加药物的情况下，NMDA反应在海马或海马皮质微囊中的两条线之间没有差异。然而，高浓度的乙醇（200 mM）抑制NMDA反应在海马微囊从LS小鼠。与此相反，中等浓度的乙醇（50毫米）刺激NMDA反应分离SS小鼠海马微囊。在皮层微囊，乙醇抑制NMDA反应在两个线到同等程度。MK-801是一种NMDA受体的非竞争性阻断剂，在LS小鼠海马微囊中以低于SS小鼠的浓度阻断NMDA反应，但在两种系的海马皮质微囊中产生相似程度的NMDA反应抑制。高浓度的乙醇（200 mm）增加静息钙在海马微囊从LS小鼠，但不是在海马微囊从SS小鼠，并增加静息钙蛋白皮质微囊从两个线的小鼠分离相等。MK-801在皮层微囊中产生的静息Ca的微小变化在两个细胞系之间没有差异。这些结果表明，LS和SS小鼠的海马NMDA受体对乙醇的敏感性不同，这可能是因为在NMDA受体的MK-801位点或与MK-801位点相互作用的其他位点的变构调节差异。
Long‐Sleep (LS) and Short‐Sleep(SS) mice, selectively bred mice that differ in the duration of anesthesia produced by an acute dose of ethanol, were used to determine the possible association of differing ethanol sensitivity of brain NMDA receptors with differing sensitivity to the anesthetic effects of ethanol in vivo. NMDA receptor‐mediated responses were determined by measurement ofl‐glutamate‐stimulated increases in free intracellular calcium concentration (Cal) using the fluorescent indicator for Ca1, Indo 1, in microsacs (a cell‐free brain membrane vesicle preparation) isolated from hippocampi or cerebral cortices of the two mouse lines. In the absence of added drugs, NMDA responses did not differ between the two lines in hippocampal or cerebrocortical microsacs. However, a high concentration of ethanol (200 mm) inhibited NMDA responses in hippocampal microsacs from LS mice. In contrast, a moderate concentration of ethanol (50 mm) stimulated NMDA responses in hippocampal microsacs isolated from SS mice. In cerebrocortical microsacs, ethanol inhibited NMDA responses in the two lines to an equivalent degree. MK‐801, a noncompetitive blocker of NMDA receptors, blocked NMDA responses at lower concentrations in hippocampal microsacs from LS mice than in SS mice, but produced a similar degree of inhibition of NMDA responses in cerebrocortical microsacs from the two lines. A high concentration of ethanol (200 mm) increased resting Ca1in hippocampal microsacs from LS mice but not in hippocampal microsacs from SS mice, and increased resting Calin cerebrocortical microsacs isolated from both lines of mice equally. The small change in resting Ca, produced by MK‐801 in cerebrocortical microsacs did not differ between the two lines. These results show that hippocampal NMDA receptors of LS and SS mice differ in their sensitivity to ethanol, possibly because of differences in allosteric modulation at the MK‐801 site or some other site that interacts with the MK‐801 site of the NMDA receptor.