CYTOSOLIC-FREE CA2+ OSCILLATIONS INDUCED BY DIADENOSINE 5',5'''-P-1,P-3-TRIPHOSPHATE AND DIADENOSINE 5',5'''-P-1,P-4-TETRAPHOSPHATE IN SINGLE-RAT HEPATOCYTES ARE INDISTINGUISHABLE FROM THOSE INDUCED BY ADP AND ATP RESPECTIVELY

Diadenosine 5',5(m)-P-1,P-3-triphosphate (Ap(3)A) and diadenosine 5',5(m)-P-1,P-4-tetraphosphate (Ap(4)A) induce distinctive patterns of [Ca2+](i) oscillations in single rat hepatocytes. We show here that [Ca2+](i) oscillations induced by Ap(3)A and ADP are indistinguishable and that [Ca2+](l) oscillations induced by Ap(4)A closely resemble those induced by ATP. These similarities embrace the following: (1) ADP and Ap(3)A invariably induce [Ca2+](i) transients of short duration (approx. 9 s). Ap(4)A, like ATP, can induce, depending upon the individual cell, either transients of short duration (approx. 9 s), transients of much longer duration or a mixture of short and long transients within a single response. We show here that the pattern of oscillations induced by Ap(4)A is similar to that induced by ATP in the same hepatocyte. (2) Elevated intracellular cyclic AMP concentration modulates Ap(3)A-induced transients, like ADP-induced transients, through an increase in both the peak [Ca2+](i) and the frequency of the transients. In contrast, Ap(4)A-induced transients, like ATP-induced transients, develop an increased duration or a sustained rise in [Ca2+](i), with no rise in peak [Ca2+](i). (3) Ap(3)A-induced transients, like ADP-induced transients, are abolished by low concentrations of the phorbol ester 4 beta-phorbol 12,13-dibutyrate (PDB; 5-10 nM), whereas long Ap(4)A-induced transients, like long ATP-induced transients, are refractory to high concentrations of PDB (100 nM). We propose that the [Ca2+](i) oscillations induced in rat hepatocytes by Ap(4)A are mediated by the same purinoceptor that mediates the effects of ADP, whereas the oscillations induced by Ap(4)A are mediated by the same purinoceptor(s) that mediate the effects of ATP.