Regulation of stimulatory adenylyl cyclase signaling during forskolin-induced differentiation of mouse neuroblastoma x rat glioma (NG108-15) cells.

Chronic exposure of neuroblastoma x glioma (NG108-15) cells to substances that elevate intracellular cAMP levels results in morphological differentiation into a more neuronal-like phenotype. Here we report that forskolin-induced differentiation is accompanied by a biphasic regulation of stimulatory adenylyl cyclase (AC) signaling. While 1 day of forskolin exposure produces an initial increase in basal, [AIF4](-)-, and prostaglandin E1 (PGE1)-stimulated AC activities, stimulatory signal transduction is substantially reduced after complete differentiation of the cells (6 days). Western blot analysis revealed that these functional changes correlate well with changes in the quantity of G(s)alpha, the stimulatory component of AC. Additional forskolin-induced adaptations were found for PGE1 receptors, inhibitory G proteins and AC. These data demonstrate that neuronal differentiation of NG108-15 cells is associated with complex regulatory changes within the stimulatory PGE1 receptor system.