Open AccessProstaglandin D 2 and adenosine as endogenous somnogens
Author(s) -
URADE Yoshihiro
Publication year - 2011
Publication title -
sleep and biological rhythms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.371
H-Index - 30
eISSN - 1479-8425
pISSN - 1446-9235
DOI - 10.1111/j.1479-8425.2010.00470.x
Subject(s) - histaminergic , adenosine , medicine , endocrinology , basal forebrain , adenosine a2a receptor , biology , adenosine receptor , chemistry , receptor , agonist , cholinergic
Prostaglandin D 2 (PGD 2 ) is the most potent endogenous sleep‐promoting substance thus far reported. We have extensively studied its action mechanism at the molecular level. PGD 2 is produced by lipocalin‐type PGD synthase, which is dominantly localized in the leptomeninges, choroid plexus, and oligodendrocytes in the brain; and it is secreted into the cerebrospinal fluid and stimulates DP 1 receptors localized in the arachnoid membrane of the ventral surface from the basal forebrain to the hypothalamus to increase the extracellular concentration of adenosine as a paracrine sleep‐promoting molecule. Adenosine diffuses into the brain parenchyma, suppresses cholinergic arousal neurons in the basal forebrain via adenosine A 1 receptors, activates sleep‐active neurons in the ventrolateral preoptic area via adenosine A 2A receptors, and concomitantly suppresses the histaminergic arousal center in the tuberomammillary nucleus through GABAergic and galaninergic inhibitory projections. Administration of an inhibitor of lipocalin‐type PGD synthase (SeCl 4 ), an antagonist of DP 1 receptors (ONO‐4127Na) or an antagonist of adenosine A 2A receptors (caffeine) results in sleep inhibition in rats and mice, indicating that the PGD 2 –adenosine system is crucial for the maintenance of physiological sleep.