title: Cholecystokinin-A receptors regulate photic input pathways to the circadian clock.
abstract: Daily behaviors are strongly dominated by internally generated circadian rhythms, but the underlying mechanisms remain unclear. In mammals, photoentrainment of behaviors to light-dark cycles involves signaling from both intrinsically photosensitive retinal ganglion cells and classic photoreceptor pathways to the suprachiasmatic nucleus (SCN). How classic photoreceptor pathways work with the photosensitive ganglion cells, however, is not fully understood. Although cholecystokinin (CCK) peptide has been shown to be present in a variety of vertebrate retinas, its function at a systems level is also unknown. In the present study we examined a possible role of CCK-A receptors in photoentrainment using CCK-A receptor knockout mice. The lacZ reporter gene within a gene-knockout cassette revealed precise localization of CCK-A receptors in the circadian clock system. We demonstrated that CCK-A receptors were located predominately on glycinergic amacrine cells but were rarely found on SCN neurons. Moreover, Ca(2+) imaging analysis demonstrated that the CCK-A agonist, CCK-8 sulfate (CCK-8s), mobilized intracellular Ca(2+) in amacrine cells but not glutamate-receptive SCN neurons. Furthermore, light pulse-induced mPer1/mPer2 gene expression in SCN, behavioral phase shifts, and the pupillary reflex were significantly reduced in CCK-A receptor knockout mice. These data indicate a novel function of CCK-A receptors in the nonimage-forming photoreception presumably via amacrine cell-mediated signal transduction pathways.
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Takao
authors: T
authors: Shimazoe
authors: Mitsutaka
authors: M
authors: Morita
authors: Shinichiro
authors: S
authors: Ogiwara
authors: Tomoyoshi
authors: T
authors: Kojiya
authors: Junpei
authors: J
authors: Goto
authors: Masaki
authors: M
authors: Kamakura
authors: Takahiro
authors: T
authors: Moriya
authors: Kazuyuki
authors: K
authors: Shinohara
authors: Soichi
authors: S
authors: Takiguchi
authors: Akira
authors: A
authors: Kono
authors: Kyoko
authors: K
authors: Miyasaka
authors: Akihiro
authors: A
authors: Funakoshi
authors: Masayuki
authors: M
authors: Ikeda
mesh_terms: D025042:Amacrine Cells / Q000502:physiology*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D008027:Light; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009043:Motor Activity / Q000528:radiation effects; D043886:Receptor, Cholecystokinin A / Q000172:deficiency / Q000502:physiology*; D012025:Reflex, Pupillary / Q000502:physiology; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000502:physiology / Q000528:radiation effects
chemical_list: C090019:8-sulfocholecystokinin octapeptide; D043886:Receptor, Cholecystokinin A; D012844:Sincalide