Reduction of acetylcholine-activated current by low concentrations of extracellular adenosine 5'-triphosphate

Effects of adenosine 5'-triphosphate (ATP) on ionic currents activated by acetylcholine (ACh) were investigated using rat pheochromocytoma PC12 cells and Xenopus oocytes expressing nicotinic receptors. In PC12 cells, ATP (10 nM to 1 microM) inhibited an inward current activated by ACh in not all but about 60% of cell batches. The ACh-activated current was also inhibited by ATP in Xenopus oocytes and, with a subunit combination of alpha 3 plus beta 4, the inhibition was observed at concentration as low as 100 fM. Uridine 5'-triphosphate (UTP) induced a similar inhibition of the ACh-activated current both in PC12 cells and Xenopus oocytes. These and other properties suggest that the current reduction by ATP is not mediated through conventional P2-purinoceptors.