Urade Y, Hayaishi O
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Japan.
Biochim Biophys Acta. 1999 Jan 4;1436(3):606-15. doi: 10.1016/s0005-2760(98)00163-5.
Prostaglandin (PG) D2 is recognized as the most potent endogenous sleep-promoting substance whose action mechanism is the best characterized among the various sleep-substances thus far reported. The PGD2 concentration in rat cerebrospinal fluid (CSF) shows a circadian change coupled to the sleep-wake cycle and elevates with an increase in sleep propensity during sleep deprivation. Lipocalin-type PGD synthase is dominantly produced in the arachnoid membrane and choroid plexus of the brain, and is secreted into the CSF to become beta-trace, a major protein component of the CSF. The PGD synthase as well as the PGD2 thus produced circulates in the ventricular system, subarachnoidal space, and extracellular space in the brain system. PGD2 then interacts with DP receptors in the chemosensory region of the ventro-medial surface of the rostral basal forebrain to initiate the signal to promote sleep probably via the activation of adenosine A2A receptive neurons. The activation of DP receptors in the PGD2-sensitive chemosensory region results in activation of a cluster of neurons within the ventrolateral preoptic area, which may promote sleep by inhibiting tuberomammillary nucleus, the source of the ascending histaminergic arousal system.
前列腺素（PG）D2被认为是最有效的内源性促睡眠物质，其作用机制在迄今为止报道的各种睡眠物质中最为明确。大鼠脑脊液（CSF）中的PGD2浓度呈现出与睡眠-觉醒周期相关的昼夜节律变化，并且在睡眠剥夺期间随着睡眠倾向的增加而升高。脂质运载蛋白型PGD合酶主要在脑的蛛网膜和脉络丛中产生，并分泌到脑脊液中成为β-痕迹蛋白，这是脑脊液的主要蛋白质成分。如此产生的PGD合酶以及PGD2在脑室系统、蛛网膜下腔和脑系统的细胞外空间中循环。然后，PGD2与延髓基底部前脑腹内侧表面化学感受区域中的DP受体相互作用，可能通过激活腺苷A2A受体神经元来启动促进睡眠的信号。PGD2敏感化学感受区域中DP受体的激活导致腹外侧视前区内一群神经元的激活，这可能通过抑制结节乳头体核来促进睡眠，结节乳头体核是上行组胺能觉醒系统的来源。
