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

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 [Ca 2+](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 i nduced by ATP. These similarities embrace the following: (1) ADP and A p(3)A invariably induce [Ca2+](i) transients of short duration (approx . 9 s). Ap(4)A, like ATP, can induce, depending upon the individual ce ll, either transients of short duration (approx. 9 s), transients of m uch longer duration or a mixture of short and long transients within a single response. We show here that the pattern of oscillations induce d 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-i nduced transients, like ADP-induced transients, through an increase in both the peak [Ca2+](i) and the frequency of the transients. In contr ast, Ap(4)A-induced transients, like ATP-induced transients, develop a n 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 trans ients, 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 c oncentrations of PDB (100 nM). We propose that the [Ca2+](i) oscillati ons induced in rat hepatocytes by Ap(4)A are mediated by the same puri noceptor that mediates the effects of ADP, whereas the oscillations in duced by Ap(4)A are mediated by the same purinoceptor(s) that mediate the effects of ATP.