Adenosine 5'-triphosphate independent secretion from PC12 pheochromocytoma cells

PC12 is a clonal line of rat pheochromocytoma. The cells secrete dopamine and acetylcholine by a Ca2+-dependent process. The requirement for adenosine 5'-triphosphate (ATP) in secretion from PC12 was investigated. Cellular levels of ATP were decreased by brief treatments with inhibitors of glycolysis or oxidative phosphorylation. In order to deplete ATP stores below 40% of control values during a 5-min treatment with these compounds, it was necessary to inhibit both glycolysis and oxidative phosphorylation. Depletion of ATP pools to as little as 10% of control values did not result in any inhibition of dopamine or acetylcholine release evoked by 55 mM K+ or by carbachol. Rather, in many cases spontaneous and evoked releases were significantly increased under these conditions. The release observed in ATP-depleted cells was Ca2+ dependent. The data indicate that, unlike the situation with most other secretory cells, secretion from PC12 is independent of ATP. In PC12 some proteins involved in the secretion process may be altered so as to make the process independent of ATP; this may be due to the fact that PC12 is a tumor cell line. Phosphotyrosine-containing proteins, which are present in some other tumor cells, were not found in PC12.