CYTOSOLIC CALCIUM RESPONSES TO EXTRACELLULAR ADENOSINE 5',5'''-P-1,P-4-TETRAPHOSPHATE IN PC12 CELLS

Binding of adenosine 5',5'''-P-1,P-4-tetraphosphate (Ap(4)A) to a puri noceptor on nerve growth factor-differentiated (NGF) pheochromacytoma (PC12) cells modulated cytosolic Ca2+ levels. Both Ap(4)A and ATP elic ited an influx of extracellular Ca2+, but both the sensitivity of the response and the flux profile were different. Preincubation of the PC1 2 cells with the compounds adenosine 5'-O-(2-thio)diphosphate (ADP-bet a-S) and periodate-oxidized ATP had differential effects upon the Ap(4 )A and ATP-induced response. These results indicate that Ap,A and ATP were either interacting with distinct purinoceptor subclasses or with the same purinoceptor with differing affinities. Simultaneous depolari zation and application of either Ap(4)A or ATP to the PC12 cells induc ed an additive effect on the calcium flux. Preincubation with verapami l negated the effects of depolarization without significantly modifyin g the ligand-elicited Ca2+ fluxes, suggesting the presence of Ap,A lig and-gated channels that may function as modulators of PC12 cell functi on.