Selective and competitive antagonism by suramin of ATP-stimulated catecholamine-secretion from PC12 phaeochromocytoma cells

1. Suramin, a putative P₂-antagonist, (10 to 300 μM) inhibited the adenosine 5'-triphosphate (ATP)-stimulated secretion of [³H]-noradrenaline or endogenous dopamine from phaeochromocytoma PC12 cells in a concentration-dependent manner. Suramin (300 μM) did not affect the dopamine-secretion stimulated by high K⁺ or nicotine. 2. Suramin shifted the concentration-response curve for ATP to the right. The antagonism was competitive with a pA₂ value of 4.52. 3. ATP also stimulated an increase in intracellular Ca²⁺ concentration as determined by fura-2 methods. Suramin antagonized this effect over the same concentration range that antagonized the ATP-stimulated catecholamine secretion. 4. These results suggest that suramin can be used as a selective and competitive antagonist of ATP in experiments concerning mechanisms of catecholamine-secretion.