Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin (PG) D2 has been proposed to be essential for the initiation and maintenance of the physiological sleep of rats because intracerebroventricular administration of selenium tetrachloride (SeCl4), a selective inhibitor of PGD synthase (PGDS), was shown to reduce promptly and effectively the amounts of sleep during the period of infusion. However, gene knockout (KO) mice of PGDS and prostaglandin D receptor (DP1R) showed essentially the same circadian profiles and daily amounts of sleep as wild-type (WT) mice, raising questions about the involvement of PGD2 in regulating physiological sleep. Here we examined the effect of SeCl4 on the sleep of WT and KO mice for PGDS and DP1R and that of a DP1R antagonist, ONO-4127Na, on the sleep of rats. The i.p. injection of SeCl4 into WT mice decreased the PGD2 content in the brain without affecting the amounts of PGE2 and PGF(2alpha). It inhibited sleep dose-dependently and immediately after the administration during the light period when mice normally sleep, increasing the wake time; and the treatment with this compound resulted in a distinct sleep rebound during the following dark period. The SeCl4-induced insomnia was observed in hematopoietic PGDS KO mice but not at all in lipocalin-type PGDS KO, hematopoietic and lipocalin-type PGDS double KO or DP1R KO mice. Furthermore, the DP1R antagonist ONO-4127Na reduced sleep of rats by 30% during infusion into the subarachnoid space under the rostral basal forebrain at 200 pmol/min. These results clearly show that the lipocalin-type PGDS/PGD2/DP1R system plays pivotal roles in the regulation of physiological sleep.
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PMID:Lipocalin-type prostaglandin D synthase produces prostaglandin D2 involved in regulation of physiological sleep. 1709 43

Prostaglandin (PG) D2 and adenosine are potent endogenous somnogens and their sleep-inducing mechanisms are well characterized. We examined the contribution of these somnogens to physiological sleep by the combination of pharmacological tools and gene-knockout (KO) mice. Complete insomnia was observed in wild-type mice after an intraperitoneal injection of SeCl4, an inhibitor of PGD synthase (PGDS), or caffeine, an antagonist of adenosine A2A receptors. The SeCl4-induced insomnia was not observed in PGDS- or DP1 receptor-KO mice and the caffeine-induced insomnia, in A(2A) receptor-KO mice. A DP1 antagonist, ONO-4127Na, reduced sleep of rats by 30% during infusion into the subarachnoid space of the basal forebrain. These results indicate that the PGD2/ adenosine system plays a critical role in the regulation of physiological sleep.
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PMID:[Molecular mechanisms of insomnia]. 1976 29