INHIBITION BY ZN2+ OF URIDINE 5'-TRIPHOSPHATE-INDUCED CA2+-INFLUX BUT NOT CA2+-MOBILIZATION IN RAT PHEOCHROMOCYTOMA CELLS

1 Uridine 5'-triphosphate (UTP)-evoked increase in intracellular Ca2+ concentration ([Ca](i)) and release of dopamine were investigated in rat phaeochromocytoma PC12 cells. UTP (1-100 mu M) evoked an increase in [Ca](i) in a concentration-dependent manner. This response was decreased to about 30% by extracellular Ca2+-depletion, but not abolished. This [Ca](i) rise was mimicked by 100 mu M ATP but not by 100 mu M 2-methyl-thio-ATP or alpha,beta-methylene-ATP in the absence of external Ca2+, suggesting that the response was mediated by P-2u purinoceptors, a subclass of P-2-purinoceptors. 2 The UTP-evoked [Ca](i) rise consisted of two components; a transient and a sustained one. When external Ca2+ was removed, the sustained component was abolished while the transient component was decreased by about 70% but did not disappear. These results suggest that UTP induces Ca2+-mobilization and, subsequently, Ca2+-influx. 3 The UTP-evoked increase in [Ca](i) was not affected by Cd2+ (100 and 300 mu M) or nicardipine (30 mu M), inhibitors of voltage-gated calcium channels, but was significantly inhibited by Zn2+ (10-300 mu M) in the presence of external Ca2+, Zn2+, however, did not affect the Ca2+ response to UTP in the absence of external Ca2+. 4 UTP (30 mu M-1 mM) evoked the release of dopamine from the cells in a concentration-dependent manner. This dopamine release was abolished by Ca2+-depletion or Zn2+ but not by Cd2+ or nicardipine. 5 Taken together, the data demonstrate that UTP stimulates P-2U-purinoceptors and induces a rise in [Ca](i) both by Ca2+-mobilization and Ca2+-influx in PC12 cells. The dopamine release evoked by UTP requires external Ca2+ which may enter the cells through pathways sensitive to Zn2+ but insensitive to Cd2+ or nicardipine.