Regulation of differentiation of PC12 cells by nerve growth factor

Abstract

The effect of NGF from bovine seminal plasma on the adenylate cyclase system of pheochromocytoma PC12 cell line was studied. It was shown that the elevation of the intracellular level of cAMP caused the NGF-like morphological differentiation of PC12 cells cultured in the serum-free medium. This effect was very transitory because of the compensatory action of phosphodiesterase of cAMP, the biosynthesis of which was induced by the elevated level of intracellular cAMP. Inhibition of the adenylate cyclase activity in the membrane preparation of PC12 cells was observed. This inhibition can be a result of a decrease in the level of endogenous ADP-ribosylation which was detected after incubation of cells with NGF. The parameters of this process were investigated. It was demonstrated that morphological differentiation of PC12 cells can be induced by serotonin (neurotransmitter), l-carnosine (dipeptide) and retinoic acid (vitamin A derivative). The possible mechanisms of action of these substances were suggested. It was shown that serotonin inhibited adenylate cyclase of PC12 cells, whereas the combined action of NGF and serotonin led to the activation of the enzyme. The hypothetic mechanism of this process was proposed.