Some P2 purinergic agonists increase cytosolic calcium but not inositol 1,4,5-trisphosphate in isolated rat hepatocytes.

Based on the capacity to increase IP3 (inositol 1,4,5-trisphosphate), P2 purinergic agonists can be subdivided into two classes: ATP, ADP, UTP, 2deoxyATP, NAD and GTP significantly increased IP3 levels whereas ADP beta S, 2MeSATP, NADP, alpha, beta MeATP, beta, gamma MeATP and ATP alpha S had only a minor, non-significant effect. Irrespective of their potency to increase IP3, all agonists were full glycogenolytic agonists and they all increased cytosolic calcium. With ATP and NAD, IP3 increasing agonists, and 2MeSATP and ADP beta S, non-IP3 increasing agonists, we found that the initial calcium response appeared to be an 'all or none' phenomenon, small amounts of the agonists being either ineffective or equally effective as high amounts. The minimal amount of an agonist needed to initiate a calcium increase and to promote glycogenolysis was very similar. In the absence of extracellular calcium, both groups of purinergic agonists (tested with ATP and 2MeSATP) were equally able to release calcium from intracellular stores. Cells with emptied intracellular calcium stores rapidly took up extracellular calcium upon treatment with ATP or 2MeSATP, the latter being the most potent. It seems therefore that all nucleotides tested increased cytosolic calcium and activated phosphorylase in a very similar way but some nucleotides had no effect on the levels of IP3.