Nerve growth factor‐induced stimulation of α‐aminoisobutyric acid uptake in PC12 cells: Relationship to plasma membrane receptor occupancy

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Abstract
Nerve growth factor (NGF) stimulates the uptake rate of the nonmetabolized amino acid α‐aminoisobutyric acid (AIB) in the clonal PC12 pheochromocytoma cell line by 40–70%. This effect reaches a maximum after a 1‐hour incubation with the hormone and then drops over 50%, reaching a minimum after 4 hours of NGF administration. Longer exposure to the hormone leads to a gradual rise in stimulation, and by 24 hours, the cells regain about 80% of the original 1‐hour rate. Results of NGF‐binding studies indicate that stimulation of AIB uptake follows closely behind the amount of NGF bound to the low‐affinity NGF receptors. Dose‐response experiments indicate that full stimulation occurs biphasically. Within the NGF concentration range of 0.1 ng/ml to 1 ng/ml, the AIB uptake rate is 30% of the maximum 1‐hour response. At 2.5 ng/ml NGF, the stimulation jumps to about 75% maximal response while 100% response is reached between 5 ng/ml and 50 ng/ml NGF. We suggest that the two states of the NGF plasma membrane receptor on PC12 cells may both be involved in mediating NGF stimulation of AIB uptake.