Adenine dinucleotide-mediated activation of glycogen phosphorylase in isolated liver cells

The ability of purine nucleotides (e.g. ATP) to cause a dose-dependent activation of glycogen phosphorylase in isolated liver cells is well known. These agents mediate their effects through interaction with specific P2-purinoceptors in the plasma membrane. We have investigated the ability of a range of synthetic and naturally occurring adenine dinucleotides to cause a similar stimulation of glycogen phosphorylase activity in isolated rat liver cells. Our results indicate that Ap3A and Ap4A, the most abundant naturally occurring adenine dinucleotides, cause a dose-dependent activation of glycogen phosphorylase similar to that observed with ATP. Similar responses were seen with Ap5A, Ap6A and a series of phosphorothioate analogues. In contrast, the response to phosphonate analogues depended on the position of the P-C-P bridge. The dinucleotides appear to exert their effects directly, rather than through hydrolytic products such as adenosine and/or ATP. The possibility that adenine dinucleotides are physiologically significant extracellular purinergic effectors is discussed in the light of these observations.