Brain lipids that induce sleep are novel modulators of 5-hydroxytryptamine receptors
Brain lipids that induce sleep are novel modulators of 5-hydroxytryptamine receptors
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DOI：
10.1073/pnas.93.15.8078
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发表时间：
1996-07-23
影响因子：
11.1
通讯作者：
Harris, RA
中科院分区：
文献类型：
--
作者：
HuidobroToro, JP;Harris, RA
最近从睡眠剥夺动物的脑脊液中分离出脂肪酸的酰胺衍生物，发现可诱导大鼠睡眠。为了确定哪些脑受体可能对这些新的神经调节剂敏感，我们在非洲爪蟾卵母细胞中表达的一系列受体上进行了测试，顺式9,10-八烯酰胺（ODA）显著增强了5-羟色胺（5-HT）对5-HT2A和5-HT2C受体的作用，但这种作用没有被油酸和反式9,10-八烯酰胺等相关化合物共享。ODA在低至1 nM的浓度下具有活性。饱和类似物十八胺抑制而不是增强5-HT2C反应。ODA对其他受体，包括毒菌碱胆碱能、代谢性谷氨酸、GABA(A)、n -甲基- d -天冬氨酸或α -氨基-3-羟基-5-甲基-4-异氧唑丙酸受体没有影响或只有微弱影响。ODA和相关脂质调节5-HT2受体可能代表了一种新的调节受体的机制，这些受体激活G蛋白，从而在警觉性、睡眠和情绪中发挥作用，同时也干扰这些状态。
Amide derivatives of fatty acids were recently isolated from cerebrospinal fluid of sleep-deprived animals and found to induce sleep in rats. To determine which brain receptors might be sensitive to these novel neuromodulators, we tested them on a range of receptors expressed in Xenopus oocytes, cis-9,10-Octadecenamide (ODA) markedly potentiated the action of 5-hydroxytryptamine (5-HT) on 5-HT2A and 5-HT2C receptors, but this action was not shared by related compounds such as oleic acid and trans-9,10-octacenamide. ODA was active at concentrations as low as 1 nM. The saturated analog, octadecanamide, inhibited rather than potentiated 5-HT2C responses. ODA had either no effect or only weak effects on other receptors, including muscarinic cholinergic, metabotropic glutamate, GABA(A), N-methyl-D-asparate, or alpha-amino-3-hydroxy-5-methyl-4-isoxozolepropionic acid receptors, Modulation of 5-HT2 receptors by ODA and related lipids may represent a novel mechanism for regulation of receptors that activate G proteins and thereby play a role in alertness, sleep, and mood as sell as disturbances of these states.