A cyclic AMP-regulated negative feedforward system for neuritogenesis revealed in a neuroblastoma × glioma hybrid cell line

We examined the role of second messengers during the neuritogenesis that accompanies neuronal differentiation in a neuroblastoma × glioma hybrid cell line (NG108-15). NG108-15 cells extended neurites after treatment with dibutyryl cyclic AMP. This dibutyryl cyclic AMP treatment evoked the synthesis of voltage-dependent Ca²⁺ channel proteins in the cells. The number of neurites was decreased by Ca²⁺ influx under condition of high K⁺. Interestingly, the increase of neurites stimulated by dibutyryl cyclic AMP and the decrease of neurites caused by high K⁺ were both reversible. This is the first study to demonstrate that cyclic AMP regulates a negative feedforward system for neuritogenesis, which links with Ca²⁺ signaling. Such a dual role of cyclic AMP may play an important part in precise neurite targeting.