ADENOSINE 5'-[ALPHA-BETA-METHYLENE]TRIPHOSPHATE POTENTIATES THE OSCILLATORY CYTOSOLIC CA2+ RESPONSES OF HEPATOCYTES TO ATP, BUT NOT TO ADP

Single rat hepatocytes microinjected with aequorin generate oscillatio ns in cytosolic free Ca2+ concentration ([Ca2+]i) when stimulated with agonists acting through the phosphoinositide signalling pathway. The duration of these transients has been shown to be characteristic of th e stimulating agonist, so that transients of very different duration c an be induced in the same individual hepatocyte by different agonists. In a previous study we have shown that ADP and ATP, which are believe d to act through a single P2y-purinoceptor species, elicit very differ ent [Ca2+], responses in most of the hepatocytes. We have interpreted this as evidence for two Ca2+-mobilizing purinoceptors. The methylated derivative of ATP, adenosine 5'-[alphabeta-methylene]-triphosphate (p p[CH2]pA), is only a weak P2y-purinoceptor agonist. When 100 muM pp[CH 2]pA was supplied to aequorin-injected hepatocytes, there was no effec t on [Ca2+]. However, 25 muM pp[CH2]pA co-supplied with ATP causes a p otentiation of the [Ca2+]i response in most of the hepatocytes. The ef fect was specific for ATP-induced transients; [Ca2+]i transients induc ed by other agonists, and importantly by ADP, were not affected by add ition of pp[CH2]pA. This further illustrates differences in the action s of ADP and ATP, strengthening the argument for separate receptors fo r these nucleotides.