We characterized the secretion of amyloid precursor protein (APP) in rat primary neurons and conditionally immortalized central nervous system (CNS) derived progenitor cell lines, to evaluate their suitability as models for studies on APP metabolism. We observed that primary cells dissociated from different regions of the embryonic brain secreted progressively more APP during in vitro maturation. The increase in basal secretion resulted in an offset of the response to protein kinase C (PKC) activated secretion and was correlated with an increased PKC alpha expression. The same type of analysis was performed on CNS derived conditionally immortalized cells whose growth potential becomes restricted upon shifting of the culture conditions to a non-permissive temperature (39 degrees C), an event that coincides with their progression toward differentiation. With a pattern consistent with that observed in primary neurons, conditionally immortalized cells exposed to 39 degrees C showed an offset of the secretory response to activation by PdBu and also an increased expression of PKC alpha. These data suggest that APP secretion and its regulation in CNS derived cells is influenced by the proliferative status of the cells.