Cytosolic calcium responses to extracellular adenosine 5',5" '-P1,P4-tetraphosphate in PC12 cells

Binding of adenosine 5',5" '-P1,P4-tetraphosphate (Ap4A) to a purinoceptor on nerve growth factor-differentiated (NGF) pheochromacytoma (PC12) cells modulated cytosolic Ca2+ levels. Both Ap4A and ATP elicited an influx of extracellular Ca2+, but both the sensitivity of the response and the flux profile were different. Preincubation of the PC12 cells with the compounds adenosine 5'-0-(2-thio)diphosphate (ADP-beta-S) and periodate-oxidized ATP had differential effects upon the Ap4A and ATP-induced response. These results indicate that Ap4A and ATP were either interacting with distinct purinoceptor subclasses or with the same purinoceptor with differing affinities. Simultaneous depolarization and application of either Ap4A or ATP to the PC12 cells induced an additive effect on the calcium flux. Preincubation with verapamil negated the effects of depolarization without significantly modifying the ligand-elicited Ca2+ fluxes, suggesting the presence of Ap4A ligand-gated channels that may function as modulators of PC12 cell function.