Extracellular adenosine 5'-triphosphate-evoked norepinephrine secretion not relating to voltage-gated Ca channels in pheochromocytoma PC12 cells.

Characteristics of extracellular ATP-stimulated norepinephrine (NE) secretion were investigated by the batch method in relation to membrane current measured with the whole cell voltage-clamp technique. Extracellular ATP stimulated [3H]NE secretion from PC12 cells in a concentration range from 10 microM to 1 mM. The maximal effect of ATP was about 5 times larger than that of nicotine. ATP-stimulated secretion was extracellular Ca-dependent, but it was not inhibited by the Ca-channel blockers, cadmium (300 microM) or nicardipine (10 microM). Extracellular ATP activated an inward current in PC12 cells and the peak amplitude of the current was about 5 times larger than that activated by nicotine. These findings suggest that extracellular ATP activates receptor-operated channels and causes NE secretion.