Department of Molecular Pharmacology, University of Tsukuba, Tsukuba, Japan.
Sleep. 2011 Jan 1;34(1):31-7. doi: 10.1093/sleep/34.1.31.
Neuropeptide B (NPB) and neuropeptide W (NPW) are two recently identified neuropeptides that act as endogenous ligands to orphan G protein coupled receptors, GPR7 and GPR8. In rodents, the GPR8 ortholog is absent and both NPB and NPW function exclusively through GPR7. Although NPB and NPW are implicated in the regulation of feeding behavior, endocrine function, and pain sensation, their physiological role is incompletely understood.
NPB or saline was administered into the lateral ventricle of mice during both the light and dark periods. In separate experiments, spontaneous locomotor activity or EEG and EMG were recorded after intracerebroventricular (i.c.v). injection. To confirm the involvement of GPR7 in NPB-induced responses, GPR7 knockout mice were also subjected to i.c.v. injections.
NPB injections reduced locomotor activity during the dark period, but not during the light period. EEG and EMG recordings in freely moving mice revealed that NPB injection decreased the time spent in the waking state and increased the time spent in slow wave sleep (SWS) during the dark period. The time spent in paradoxical sleep was unaffected. The spectral power of NPB-induced SWS was indistinguishable from that of physiological SWS. The NPB-induced increase in SWS was not observed in GPR7 knockout mice.
These results suggest that NPB induced physiological SWS through GPR7 and that NPB and GPR7 may have a role in modulating the occurrence of sleep and wakefulness.
神经肽 B(NPB)和神经肽 W(NPW)是两种最近被鉴定出的神经肽,作为孤儿 G 蛋白偶联受体 GPR7 和 GPR8 的内源性配体发挥作用。在啮齿动物中,GPR8 同源物缺失,NPB 和 NPW 均通过 GPR7 发挥作用。尽管 NPB 和 NPW 参与调节摄食行为、内分泌功能和疼痛感觉,但它们的生理作用尚未完全阐明。
在白天和黑夜期间,将 NPB 或生理盐水注入小鼠侧脑室。在单独的实验中,在脑室内(i.c.v.)注射后记录自发运动活动或 EEG 和 EMG。为了确认 GPR7 在 NPB 诱导的反应中的参与,还对 GPR7 敲除小鼠进行了 i.c.v. 注射。
NPB 注射减少了黑暗期的运动活动,但不减少白天的运动活动。在自由活动的小鼠中进行 EEG 和 EMG 记录显示,NPB 注射减少了清醒状态的时间,并增加了黑暗期慢波睡眠(SWS)的时间。异相睡眠的时间不受影响。NPB 诱导的 SWS 的光谱功率与生理 SWS 的光谱功率无法区分。在 GPR7 敲除小鼠中未观察到 NPB 诱导的 SWS 增加。
这些结果表明,NPB 通过 GPR7 诱导生理性 SWS,并且 NPB 和 GPR7 可能在调节睡眠和觉醒的发生中发挥作用。