title: Adenine dinucleotide-mediated activation of glycogen phosphorylase in isolated liver cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Liverpool, U.K.
authors.forename: K M
authors.initials: KM
authors.lastname: Craik
authors.forename: A G
authors.initials: AG
authors.lastname: McLennan
authors.forename: M J
authors.initials: MJ
authors.lastname: Fisher
mesh_terms: D000227:Adenine Nucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000378:metabolism; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
chemical_list: D000227:Adenine Nucleotides; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D006005:Phosphorylases; D000241:Adenosine