ELEVATED INTRACELLULAR CYCLIC-AMP EXERTS DIFFERENT MODULATORY EFFECTS ON CYTOSOLIC-FREE CA2+ OSCILLATIONS INDUCED BY ADP AND ATP IN SINGLE-RAT HEPATOCYTES

Single aequorin-injected hepatocytes respond to agonists acting via the phosphoinositide signalling pathway by the generation of oscillations in cytosolic free Ca2+ concentration ([Ca2+](free)). The duration of[Ca2+](free) transients is characteristic of the stimulating agonist. We have previously reported that ADP and ATP, which are believed to act through a single P-2y-purinoceptor species, induce very different oscillatory [Ca2+](free) responses in the majority of hepatocytes. We have interpreted these data as evidence for two separate Ca2+-mobilizing purinoceptors for these nucleotides. We show here that the elevation of intracellular cyclic AMP concentration, by the co-application of either dibutyryl cyclic AMP or 7 beta-desacetyl-7 beta-[gamma-(N-methylpiperazino)butyryl]- forskolin (L858051), exerts different modulatory effects on [Ca2+](free) oscillations induced by ADP and ATP in single rat hepatocytes. Elevated intracellular cyclic AMP levels enhance the frequency and peak [Ca-free(2+)] of transients induced by ADP. In contrast, the elevation of intracellular cyclic AMP levels in hepatocytes producing [Ca2+](free) oscillations in response to ATP stimulates either an increase in the duration of transients or a sustained rise in [Ca2+](free). The data illustrate a further difference between the oscillatory [Ca2+](free) responses of hepatocytes to ADP and ATP, thus further arguing against ADP and ATP acting via a single purinoceptor species.