Nerve growth factor-induced stimulation of alpha-aminoisobutyric acid uptake in PC 12 cells: evaluation of its biological significance.

In the clonal PC12 pheochromocytoma cell line, the observed effects of nerve growth factor (NGF) on the uptake rates of alpha-aminoisobutyric acid (AIB) depend upon the assay conditions employed. In orthodox uptake assays calling for serum removal prior to the addition of AIB, 50 ng/ml NGF causes a stimulation of uptake of 62% after 40 minutes and 46% after 24-hours exposure. However, serum stimulates AIB uptake to a similar extent and the effects of serum and NGF are not additive. An uptake assay which directly measures the AIB uptake experienced by PC12 cells undergoing NGF-induced morphological differentiation was therefore employed. When compared with control cells growing in serum-containing medium, NGF-induced differentiating PC12 calls experience (1) only a transient and modest increase in AIB uptake, and (2) a significant long-term decrease in AIB uptake under conditions optimal for differentiation. It is concluded that NGF-directed neurite outgrowth is not mediated by NGF effects on amino acid uptake via the A-system.