Cholecystokinin receptor type A are involved in the circadian rhythm of the mouse retina.

The retina is the only organ projecting external light to the suprachiasmatic nucleus. Cholecystokinin receptor type A (Cckar/) is one of the essential factors for light reception in retinal cells. As there was a lack of literature on the matter, we aimed to elucidate the cause of the time-dependent phase change in clock gene expression. We found that mRNA expression in retinal cells exhibited diurnal variations. The rhythm of expression of the clock gene / in retinal cells was altered in mice. The light sensitivity of retinal cells was evaluated in wild-type mice, which showed c-Fos was activated in the ganglion cell layer more than in the inner granular layer. This increase in the number of c-Fos-positive cells was suppressed by lorglumide, a Cckar antagonist. Treatment of rat retina primary cells with lorglumide suppressed transcription, which was altered in a time-dependent manner relative to the expression. Light irradiation studies in mice did not exhibit an increase in expression in the suprachiasmatic nucleus. These results indicate that Cckar is among the factors that regulate the cycle of clock genes on the retina. knockout attenuates the light responsiveness of suprachiasmatic nucleus and reduces the expression amplitude of genes in the retina. Thus, Cckar may contribute to entrainment of the light environment and maintenance of the expression cycle of gene, which is one of the core clock genes.