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Updated: Jul 9, 2026
11:56
In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
Published on: September 28, 2017
Cholecystokinin-A receptors regulate photic input pathways to the circadian clock
Takao Shimazoe1, Mitsutaka Morita, Shinichiro Ogiwara
1Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Summary
Cholecystokinin-A (CCK-A) receptors play a crucial role in photoentrainment, influencing circadian rhythms and light-mediated responses. These receptors, found on retinal amacrine cells, are vital for signaling to the brain's circadian clock.
Area of Science:
- Neuroscience
- Chronobiology
- Ophthalmology
Background:
- Circadian rhythms govern daily behaviors, but their light-entrainment mechanisms are not fully understood.
- Mammalian photoentrainment involves retinal photoreceptors and intrinsically photosensitive retinal ganglion cells signaling to the suprachiasmatic nucleus (SCN).
- The function of cholecystokinin (CCK) peptide in the retina and its role in systems-level processes remain largely unknown.
Purpose of the Study:
- To investigate the role of CCK-A receptors in the photoentrainment of circadian rhythms.
- To determine the localization and function of CCK-A receptors within the mammalian circadian clock system.
Main Methods:
- Utilized CCK-A receptor knockout mice to assess photoentrainment.
- Employed lacZ reporter gene for precise localization of CCK-A receptors.
- Performed Ca(2+) imaging to analyze CCK-A receptor agonist effects on retinal cells.
- Measured light-induced mPer1/mPer2 gene expression, behavioral phase shifts, and pupillary reflexes.
Main Results:
- CCK-A receptors were predominantly localized on glycinergic amacrine cells, with rare expression on SCN neurons.
- CCK-A agonist (CCK-8s) mobilized intracellular Ca(2+) in amacrine cells, but not in SCN neurons.
- CCK-A receptor knockout mice exhibited significantly reduced SCN mPer1/mPer2 expression, behavioral phase shifts, and pupillary reflexes.
Conclusions:
- CCK-A receptors have a novel function in non-image-forming photoreception.
- CCK-A receptors likely mediate photoentrainment through amacrine cell-based signal transduction pathways.
- These findings elucidate a new component in the complex circuitry of circadian light entrainment.
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