OSCILLATIONS IN CYTOSOLIC-FREE CA2+ INDUCED BY ADP AND ATP IN SINGLE-RAT HEPATOCYTES DISPLAY DIFFERENTIAL SENSITIVITY TO APPLICATION OF PHORBOL ESTER

We have previously described differences in the osillatory responses of cytosolic free Ca2+ concentration ([Ca2+](i)) in hepatocytes to ADP and ATP, which we have interpreted as evidence that these two nucleotides are acting at distinct receptors. We show here that ADP- and ATP-induced oscillations are differentially sensitive to application of the phorbol ester 4 beta-phorbol 12,13-dibutyrate (PDB). ADP-induced [Ca2+](i) oscillations are abolished by low concentrations of PDB (5-10 nM), whereas ATP-induced oscillations of long duration are refractory to PDB, even at greatly elevated concentrations (100 nM). The data illustrate a further difference in the actions of ADP and ATP, strengthening the argument that these agonists are not acting at the same receptor on rat hepatocytes.