Suppression of cAMP-dependent gene expression by cholecystokinin in the hippocampus

Our previous study suggests that “the neuropeptidergic system” might promote a diversity of the mechanisms that regulate signal transmission in the hippocampus. Cholecystokinin (CCK) is the mostly expressed neuropeptide gene in the hippocampus. Here, we investigated whether CCK regulates immediate-early genes (Egr1/zif268 and Fos), critical indicators of cortical neuronal activity. We showed that CCK increased Egr1/zif268 promoter activity in a neuronal cell line, which is transfected with CCKB receptor. Unexpectedly, in living hippocampal slices, CCK significantly suppressed cAMP-induced expression of Egr1/zif268 and Fos through CCKB receptor activation. This suppression was involved in activating GABAB and cannabinoid 1 receptors. In addition to transient CCK modulation of action potentials on hippocampal principal neurons, we suggest that release of endogenous CCK might indirectly produce the suppression of cAMP-dependent gene expression in the hippocampus.

▶We examined regulation of immediate-early genes by CCK in living hippocampal slices. ▶CCK significantly suppressed cAMP-induced expression of immediate-early genes. ▶This suppression was involved in CCKB receptor activation. ▶This suppression was also involved in activating GABAB and CB1 receptors. ▶Endogenous CCK might indirectly produce this suppression in the hippocampus.