Chaurasia Shyam S, Haque Rashidul, Pozdeyev Nikita, Jackson Chad R, Iuvone P Michael
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Neurochem. 2006 Nov;99(4):1142-50. doi: 10.1111/j.1471-4159.2006.04154.x. Epub 2006 Sep 18.
cAMP signaling pathways play crucial roles in photoreceptor cells and other retinal cell types. Previous studies demonstrated a circadian rhythm of cAMP level in chick photoreceptor cell cultures that drives the rhythm of activity of the melatonin synthesizing enzyme arylalkylamine N-acetyltransferase and the rhythm of affinity of the cyclic nucleotide-gated channel for cGMP. Here, we report that the photoreceptor circadian clock generates a rhythm in Ca(2+)/calmodulin-stimulated adenylyl cyclase activity, which accounts for the temporal changes in the cAMP levels in the photoreceptors. The circadian rhythm of cAMP in photoreceptor cell cultures is abolished by treatment with the l-type Ca(2+) channel antagonist nitrendipine, while the Ca(2+) channel agonist, Bay K 8644, increased cAMP levels with continued circadian rhythmicity in constant darkness. These results indicate that the circadian rhythm of cAMP is dependent, in part, on Ca(2+) influx. Photoreceptor cell cultures exhibit a circadian rhythm in Ca(2+)/calmodulin-stimulated adenylyl cyclase enzyme activity with high levels at night and low levels during the day, correlating with the temporal changes of cAMP in these cells. Transcripts encoding two of the Ca(2+)/calmodulin-stimulated adenylyl cyclases, type 1 and type 8 (Adcy1 and Adcy8), displayed significant daily rhythms of mRNA expression under a light-dark cycle, but only the Adcy1 transcript rhythm persisted in constant darkness. Similar rhythms of Adcy1 mRNA level and Ca(2+)/calmodulin-stimulated adenylyl cyclase activity were observed in retinas of 2-week-old chickens. These results indicate that a circadian clock controls the expression of Adcy1 mRNA and Ca(2+)/calmodulin-stimulated adenylyl cyclase activity; and calcium influx into these cells gates the circadian rhythm of cAMP, a key component in the regulation of photoreceptor function.
环磷酸腺苷（cAMP）信号通路在光感受器细胞和其他视网膜细胞类型中发挥着关键作用。先前的研究表明，鸡光感受器细胞培养物中cAMP水平存在昼夜节律，该节律驱动褪黑素合成酶芳基烷基胺N - 乙酰基转移酶的活性节律以及环核苷酸门控通道对环磷酸鸟苷（cGMP）的亲和力节律。在此，我们报告光感受器昼夜节律钟产生钙（Ca²⁺）/钙调蛋白刺激的腺苷酸环化酶活性节律，这解释了光感受器中cAMP水平的时间变化。用L型钙（Ca²⁺）通道拮抗剂尼群地平处理可消除光感受器细胞培养物中cAMP的昼夜节律，而钙（Ca²⁺）通道激动剂Bay K 8644在持续黑暗中增加cAMP水平并保持昼夜节律性。这些结果表明，cAMP的昼夜节律部分依赖于钙（Ca²⁺）内流。光感受器细胞培养物在钙（Ca²⁺）/钙调蛋白刺激的腺苷酸环化酶酶活性方面表现出昼夜节律，夜间水平高，白天水平低，这与这些细胞中cAMP的时间变化相关。编码两种钙（Ca²⁺）/钙调蛋白刺激的腺苷酸环化酶，即1型和8型（Adcy1和Adcy8）的转录本，在明暗周期下显示出显著的mRNA表达每日节律，但只有Adcy1转录本节律在持续黑暗中持续存在。在2周龄鸡的视网膜中观察到Adcy1 mRNA水平和钙（Ca²⁺）/钙调蛋白刺激的腺苷酸环化酶活性的类似节律。这些结果表明，昼夜节律钟控制Adcy1 mRNA的表达和钙（Ca²⁺）/钙调蛋白刺激的腺苷酸环化酶活性；并且钙流入这些细胞控制着cAMP的昼夜节律，而cAMP是光感受器功能调节中的关键成分。
