Studies on the role of histaminergic system in orexin-induced wakefulness in rats.

组胺能系统在食欲素诱导大鼠觉醒中作用的研究。

• 批准号: 14570912
• 负责人: HONDA Kazuki
• 金额: $ 2.24万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570912/
• 关键词: Orexin; Histamine; Narcolepsy; Sleep; Pyrilamine; 睡眠覚醒; ラット; 第三脳室内連続注入; 脳波

Orexins A and B are novel neuropeptides involved in the regulation of feeding and arousal state. Orexin-containing neurons are localized in the lateral hypothalamic area and densely project to the locus coeruleus, ventral tegmental area, dorsal raphe nuclei and tuberomammillary nucleus (TMN). Previously, we reported that intracerebroventricular (icy) infusion into the third ventricle of both orexins A and B induced arousal effect in the rats. Recently, we found direct synaptic connectivity between orexin nerve terminals and histaminergic neurons in the TMN where the OX2R is abundantly expressed. Hence, orexin-induced arousal state seems to be regulated via histaminergic neurons in the TMN. In this study, we investigate the effects of icy infusion of pyrilamine (an Hi receptor antagonist) on orexin-induced wakefulness in rats. Cortical FEG and neck EMG were monitored for three consecutive days, during continuous icy saline infusion at a rate of 10 rd/h. For diurnal period, orexin A (1 n … More mol/20 ul saline) and pyrilamine (25 or 75 ug/25 ul saline) replaced the icy infusion of saline. Pyrilamine administration was started 30 mm before orexin A infusion. The icy infusion of orexin A for a 2-h period markedly increased the amount of wakefulness by 340.0 % (p<0.05) over the baseline value. Pyrilamine decreased orexin A-induced wakefulness by 85 % (p<0.05) and 58 % (p<0.05), at 25 and 75 ug/2.5-h period, respectively. Pyrilamine caused a dose-dependent decrease in the orexin A-induced arousal effect. Orexin A-induced suppression of non-REM sleep was dose-dependently reversed by pyrilamine treatment. Although pyrilamine treatment alone (75 ug) slightly decreased REM sleep, no significant difference was observed. Pyrilamine, an Hi receptor antagonist, significantly inhibited the effects of orexin A-induced wakefulness. Since orexin neurons densely innervate TMN where OX_2R is highly expressed, orexin neurons might regulate the arousal state through modulating the activity of histaminergic neurons in the TMN. Less

食欲素A和B是一种新的神经肽，参与摄食和唤醒状态的调节。食欲素神经元位于下丘脑外侧区，密集投射到蓝斑、腹侧被盖区、中缝背核和结节乳头核。以前，我们报道了侧脑室（冰）注入到第三脑室的食欲素A和B诱导唤醒作用的大鼠。最近，我们发现直接的突触连接之间的食欲素神经末梢和组胺能神经元的TMN中的OX 2 R是丰富的表达。因此，食欲素诱导的唤醒状态似乎是通过TMN中的组胺能神经元来调节的。在这项研究中，我们研究了冰输液的pyrilamine（一种Hi受体拮抗剂）对食欲素诱导的觉醒大鼠的影响。在以10 rd/h的速率连续输注冰盐水期间，连续三天监测皮层FEG和颈部EMG。在昼夜周期，食欲素A（1 n ...更多信息 mol/20 μ l盐水）和吡拉明（25或75 μ g/25 μ l盐水）代替盐水的冰冷灌注。在食欲素A输注前30分钟开始给予吡拉明。在2小时的时间内冰冷地输注食欲素A使觉醒的量比基线值显著增加340.0%（p<0.05）。吡拉明在25和75 ug/2.5-h时分别使食欲素A诱导的觉醒减少85%（p <0.05）和58%（p<0.05）。吡拉明引起食欲素A诱导的唤醒作用的剂量依赖性降低。食欲素A诱导的非REM睡眠抑制被吡拉明处理剂量依赖性地逆转。尽管单独使用吡拉明（75 μ g）治疗略微减少了REM睡眠，但没有观察到显著差异。Hi受体拮抗剂Pyrilamine显著抑制食欲素A诱导的觉醒。由于OX_2R高表达的TMN内分布着大量的食欲素神经元，因此食欲素神经元可能通过调节TMN内组胺能神经元的活性来调节觉醒状态。少

项目成果

Iwasaki Y: "Immobilization of phosphorycholine polymers to Ti-supported vinyldimethylsiyl monolyaers and reduction of albumin adsorption."Colloids and Surfaces B : Biointerfaces. 32. 77-84 (2003)

Iwasaki Y：“将磷酸胆碱聚合物固定到钛支撑的乙烯基二甲基甲硅烷基单分子上并减少白蛋白吸附。”胶体和表面 B：生物界面。

Yamanaka A, Tsujino N, Funahashi H, Honda K, Guan JJ, Wang QP, Tominaga M, Goto K, Sakurai T.: "Orexins activate his neurons in the tuberomammillary nucleus via the OX2 receptor."Biochem Biophys Res Commun. 290. 1237-1245 (2002)

Yamanaka A、Tsujino N、Funahashi H、Honda K、Guan JJ、Wang QP、Tominaga M、Goto K、Sakurai T.：“食欲素通过 OX2 受体激活结节乳头核中的神经元。”Biochem Biophys Res Commun。

Akanmu MA, Honda K, Inoue S.: "Hypnotic effects of total aqueous extracts of Vervain hastate(Verbenance) in rats."Psychiatr Clin Neurosci. 56. 309-310 (2002)

Akanmu MA、Honda K、Inoue S.：“马鞭草总水提取物对大鼠的催眠作用。”精神病学临床神经科学。

Katayama, Y., Homma, T., Honda, K., Hirai, K.: "Actions of orexin-A in the myenteric plexus of the guinea-pig small intestine"NeuroReport. 14. 1515-1518 (2003)

Katayama, Y.、Homma, T.、Honda, K.、Hirai, K.：“食欲素-A 在豚鼠小肠肌间神经丛中的作用”NeuroReport。

Hasegawa T: "Amino acid release in the rat oral pontine reticular nucleus across various vigilance states."SBR. 1. 195-198 (2003)

长谷川 T：“大鼠口腔脑桥网状核在不同警戒状态下的氨基酸释放。”SBR。