Expression of Mitochondrial Uncoupling Proteins and GABA Signaling Molecules in Unstimulated and Nerve Growth Factor–Stimulated PC12 Cells: Models for Chromaffin Cells and Sympathetic Neurons

PC12 cells are a cell line originating from rat adrenal medullary chromaffin (AMC) cells. They extend a neurite-like structure in response to nerve growth factor (NGF). Thus, unstimulated and NGF-stimulated PC12 cells are used as models for AMC cells and sympathetic ganglion cells, respectively. However, how closely unstimulated and stimulated PC12 cells resemble AMC cells and sympathetic neurons, respectively, has not been elucidated sufficiently. We explored these issues by using biochemical and immunocytochemical methods. AMC cells and PC12 cells selectively expressed uncoupling protein 3 (UCP3) and uncoupling protein 4 (UCP4), respectively, and glucocorticoid activity inhibited UCP4 expression in PC12 cells. PC12 cells expressed extremely low levels of chromaffin granule-associated proteins, whereas the amount of synaptophysin, a synaptic vesicle-associated protein, was much higher than that in the adrenal medulla. Similar to AMC cells, the muscarinic receptor type 1 was located at the cell periphery in unstimulated PC12 cells, and its expression was markedly enhanced by NGF. Furthermore, NGF stimulation abolished the expression of GABA signaling molecules in PC12 cells. The results suggest that the properties of unstimulated PC12 cells are between those of AMC cells and sympathetic ganglion cells and GABA signaling is intrinsic to AMC cells.