Selective and competitive antagonism by suramin of ATP-stimulated catecholamine-secretion from PC12 phaeochromocytoma cells.
1. Suramin, a putative P2-antagonist, (10 to 300 microM) 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 microM) 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.
Division of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
K
K
Inoue
K
K
Nakazawa
M
M
Ohara-Imaizumi
T
T
Obama
K
K
Fujimori
A
A
Takanaka
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D013498:Suramin / Q000494:pharmacology*
D002395:Catecholamines; D013498:Suramin; D000255:Adenosine Triphosphate; D002118:Calcium