Binding of 2',5'-dideoxyadenosine to brain membranes. Comparison to P-site inhibition of adenylate cyclase.
Membranes from rat cerebral cortex and striatum contain a relatively large number of high-affinity binding sites for [3H]2',5'-dideoxyadenosine, [3H]adenine arabinoside, and [3H]adenosine. The binding of [3H]2',5'-dideoxyadenosine and [3H]adenine arabinoside was virtually unaffected by relatively specific agonists and antagonists for adenosine receptors, such as 2-chloroadenosine, N6-phenylisopropyladenosine or theophylline. Binding of [3H]adenosine was partially blocked by such receptor ligands. The specific binding of all three ligands was antagonized by a variety of adenosine analogs which inhibit adenylate cyclase by interaction with the so-called P-site associated with this enzyme. However, potencies of adenosine analogs as P-site inhibitors of adenylate cyclase and as antagonists of binding do not correlate well. 5'-Methylthioadenosine had high potency and efficacy versus binding of [3H]2',5'-dideoxyadenosine but had virtually no effect on activity of adenylate cyclase. 2-Fluoroadenosine was less potent than adenosine as an antagonist of specific binding of [3H]2',5'-dideoxyadenosine, while 2-fluoroderivatives of adenosine, adenine arabinoside and adenine xylofuranoside were more potent than the parent compounds as P-site inhibitors. The significance of the binding sites for [3H]2',5'-dideoxyadenosine remains unclear, but their presence complicates the use of [3H]adenosine and certain analogs as ligands for adenosine membrane sites associated with adenylate cyclase.
D000241:Adenosine / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D003839:Deoxyadenosines / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000494:pharmacology; D014740:Vidarabine / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D003839:Deoxyadenosines; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D013806:Theophylline; D014740:Vidarabine; D000241:Adenosine