[Molecular mechanisms of insomnia].
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.
Urade
Yoshihiro
Y
Department of Molecular Behavioral Biology, Osaka Bioscience Institute.
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D055786:Gene Knockout Techniques; D051379:Mice; D015230:Prostaglandin D2 / Q000502:physiology*; D012890:Sleep / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000503:physiopathology*
D000241:Adenosine; D015230:Prostaglandin D2