目的 内源性前列腺素( prostaglandin, PG ) D2 能增加基底前脑下蛛网膜下腔内的腺苷水平,可能作用于腺苷 A 2A 受体,诱发睡眠。本实验观察腺苷 A 2A 受体特异性激动剂 CGS21680 和 PGD2 促眠作用的异同。 方法 手术插入不锈钢导管至大鼠基底前脑下蛛网膜下腔,同时埋植脑电波和肌电波记录电极,术后 2 周,经导管微量恒速灌注 PGD2 ( 200 pmol·0.2 μL-1·min-1 )或 CGS21680 ( 10 pmol·0.2 μL-1·min-1 ),同步记录脑电波和肌电波,分析睡眠量、睡眠强度及睡眠时相转换等参数。 结果 与人工脑脊液自身对照相比, PGD2 和 CGS21680 都显著增加慢波睡眠(非快动眼睡眠)量和睡眠强度,两者在时相转化和各波段时程上表现出高度的相似性。 CGS21680 增加快动眼睡眠量,而 PGD2 不引起快动眼睡眠量的增加。 结论 ■ 腺苷 A 2A 受体激动剂 CGS21680 能模拟 PGD2 诱发的慢波睡眠,提示腺苷 A 2A 受体是诱导生理性睡眠的重要靶点之一。
Abstract
OBJECTIVE To compare the sleep-wake profiles induced by endogenous prostaglandin (PG)D2 and CGS21680, an adenosine A2A receptor agonist. METHODS Under 10% chloral hydrate anesthesia [360 mg·kg-1 intraperitoneal (i.p.)], rats underwent the surgery for implantation of electrodes for electroencephalogram (EEG) and electromyogram recordings and placement of a stainless steel cannula inserted stereotaxically into the subarachnoid space under the basal forebrain for infusion of PGD2 or CGS21680. The software SleepSign was used to analyze EEG parameters, including sleep amount, sleep episode, stage transition and power density. RESULTS PGD2 and CGS21680 induced non-rapid eye movement sleep was similar to physiological sleep with the same amounts, identical patterns of sleep episode number and duration, stage transition, and power density. CONCLUSION Activation of adenosine A2A receptors by CGS21680 mimicked the somnogenic effects of PGD2.
关键词
腺苷 A 2A 受体 /
CGS21680 /
脑电图 /
前列腺素 D2 /
大鼠 /
睡眠
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Key words
adenosine A2A receptor /
CGS21680 /
electroencephalogram /
prostaglandin D2 /
rat /
sleep
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参考文献
[1] NARUMIYA S, OGOROCHI T, NAKAO K, et al. Prostaglandin D 2 in rat brain, spinal cord and pituitary: basal level and regional distribution [J]. Life Sci, 1982, 31(19): 2093-2103.
[2] QU W M, HUANG Z L, XU X H, et al. Lipocalin-type prostaglandin D synthase produces prostaglandin D2 involved in regulation of physiological sleep [J]. Proc Natl Acad Sci USA, 2006, 103(47): 17949-17954.
[3] PANDEY H P, RAM A, MATSUMURA H, et al. Concentration of prostaglandin D 2 in cerebrospinal fluid exhibits a circadian alteration in conscious rats [J]. Biochem Mol Biol Int, 1995, 37(3): 431-437.
[4] HUANG Z L, URADE Y, HAYAISHI O.Prostaglandins and adenosine in the regulation of sleep and wakefulness [J]. Curr Opin Pharmacol, 2007, 7(1): 33-38.
[5] FREDHOLM B B, AP I J, JACOBSON K A, et al. International union of pharmacology.XXV.Nomenclature and classification of adenosine receptors [J]. Pharmacol Rev, 2001, 53(4): 527-552.
[6] PORKKA-HEISKANEN T, STRECKER R E, THAKKAR M, et al. Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness [J]. Science, 1997, 276(5316): 1265-1268.
[7] RAINNIE D G, GRUNZE H C, MCCARLEY R W, et al.Adenosine inhibition of mesopontine cholinergic neurons: implications for EEG arousal [J]. Science, 1994, 263(5147): 689-692.
[8] SATOH S, MATSUMURA H, HAYAISHI O.Involvement of adenosine A 2A receptor in sleep promotion [J]. Eur J Pharmacol, 1998, 351(2): 155-162.
[9] HUANG Z L, QU W M, EGUCHI N, et al. Adenosine A 2A , but not A1, receptors mediate the arousal effect of caffeine [J]. Nat Neurosci, 2005, 8(7): 858-859.
[10] HONG Z Y, HUANG Z L, QU W M, et al.An adenosine A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats [J]. J Neurochem, 2005, 92(6): 1542-1549.
[11] TERAO A, HUANG Z L, WISOR J P, et al. Gene expression in the rat brain during prostaglandin D2 and adenosinergically-induced sleep [J]. J Neurochem, 2008, 105(4): 1480-1498.
[12] QIU M H, YUE X F , XU X H, et al. Somnogenic effects of <>L-stepholidine in mice [J]. Chin Pharmacol Bull (中国药理学通报) , 2008, 24(1): 20-23.
[13] QU W M, HUANG Z L, XU X H, et al. Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil [J]. J Neurosci, 2008, 28(34): 8462-8469.
[14] HUANG Z L, SATO Y, MOCHIZUKI T, et al. Prostaglandin E2 activates the histaminergic system via the EP4 receptor to induce wakefulness in rats [J]. J Neurosci, 2003, 23(14): 5975-5983.
[15] HUANG Z L, QU W M, LI W D, et al. Arousal effect of orexin A depends on activation of the histaminergic system [J]. Proc Natl Acad Sci USA, 2001, 98(17): 9965-9970.
[16] BORBELY A A, ACHERMANN P. Ultradian dynamics of sleep after a single dose of benzodiazepine hypnotics [J]. Eur J Pharmacol, 1991, 195(1): 11-18.
[17] MATSUOKA T, NARUMIYA S. Prostaglandin receptor signaling in disease [J]. Sci World J, 2007, 7:1329-1347.
[18] JACOBSON K A, GAO Z G. Adenosine receptors as therapeutic targets [J]. Nat Rev Drug Discovery, 2006, 5(3): 247-264.
( 收稿日期 : 2009-01-23 )
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