Cited by 201Sleep and Wakefulness ResearchCircadian rhythm and melatoninNeuroscience of respiration and sleep

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Prostaglandin D2 and sleep/wake regulation

Urade, Yoshihiro, Hayaishi, Osamu·2011·Sleep Medicine Reviews

DOI 10.1016/j.smrv.2011.08.003

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Abstract

Prostaglandin (PG) D2 is the most potent endogenous sleep-promoting substance. PGD2 is produced by lipocalin-type PGD synthase localized in the leptomeninges, choroid plexus, and oligodendrocytes in the brain, and is secreted into the cerebrospinal fluid as a sleep hormone. PGD2 stimulates DP1 receptors localized in the leptomeninges under the basal forebrain and the hypothalamus. As a consequence, adenosine is released as a paracrine sleep-promoting molecule to activate adenosine A2A receptor-expressing sleep-promoting neurons and to inhibit adenosine A1 receptor-possessing arousal neurons. PGD2 activates a center of non-rapid eye movement (NREM) sleep regulation in the ventrolateral preoptic area, probably mediated by adenosine signaling, which activation inhibits the histaminergic arousal center in the tuberomammillary nucleus via descending GABAergic and galaninergic projections. The administration of a lipocalin-type PGD synthase inhibitor (SeCl4), DP1 antagonist (ONO-4127Na) or adenosine A2A receptor antagonist (caffeine) suppresses both NREM and rapid eye movement (REM) sleep, indicating that the PGD2-adenosine system is crucial for the maintenance of physiological sleep.

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Authors: Urade, Y., & Hayaishi, O.
Corresponding author: Urade, Yoshihiro
Venue: Sleep Medicine Reviews
Publisher: Elsevier BV
Published: 2011-12
Volume: 15
Issue: 6
Pages: 411-418
ISSN: 1087-0792 (ISSN-L)
DOI: 10.1016/j.smrv.2011.08.003
OpenAlex: W2086043410
Cited by: 200
References: 70
Citations by year: 2026: 6 · 2025: 11 · 2024: 13 · 2023: 16 · 2022: 14 · 2021: 18 · 2020: 12 · 2019: 12 · 2018: 8 · 2017: 20 · 2016: 10 · 2015: 11 · 2014: 16 · 2013: 24 · 2012: 8
FWCI: 1.34
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Sleep Medicine Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: Ono Pharmaceutical
Japan Society for the Promotion of Science
Japan Science and Technology Agency
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords: prostaglandin D2, sleep regulation, sleep-wake regulation, DP1 receptor, adenosine A2A receptor, adenosine signaling, NREM sleep, REM sleep, ventrolateral preoptic area, tuberomammillary nucleus, galanin, caffeine, sleep-promoting neurons, cerebrospinal fluid
MeSH terms: Adenosine, Animals, Brain, Humans, Sleep, Sleep Stages, Wakefulness, Prostaglandin D2, Mice

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Prostaglandin D2 and sleep/wake regulation

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