MODULATION OF A 2A ADENOSINE RECEPTOR(S) BY K + ATP CHANNELS IN BOVINE BRAIN STRIATAL MEMBRANES

The modulation of adenosine receptor with K + ATP channel blocker, glibenclamide, was investigated using the radiolabeled A 2A ‐receptor selective agonist [ 3 H]CGS 21680. Radioligand binding studies in bovine brain striatal membranes (BBM) indicated that unlabeled CGS 21680 displaced the bound [ 3 H]CGS 21680 in a concentration‐dependent manner with a maximum displacement being approximately 65% at 10 −4 m . In the presence of 10 −5 m glibenclamide, unlabeled CGS 21680 increased the displacement of bound [ 3 H]CGS 21860 by approximately 28% at 10 −4 m . [ 3 H]CGS 21680 bound to BBM in a saturable manner to a single binding site ( K d =10.6±1.71n m ; B max =221.4±6.43fmol/mg of protein). In contrast, [ 3 H]CGS 21680 showed saturable binding to two sites in the presence of 10 −5 m glibenclamide; ( K d =1.3± 0.22n m ; B max =74.3±2.14fmol/mg protein; and K d =8.9±0.64n m ; B max =243.2±5.71fmol/mg protein), indicating modulation of adenosine A 2A receptors by glibenclamide. These studies suggest that the K + ATP channel blocker, glibenclamide, modulated the adenosine A 2A receptor in such a manner that [ 3 H]CGS 21680 alone recognizes a single affinity adenosine receptor, but that in the presence of glibenclamide it binds to two sites. These studies provide further insight into the interactions between K + ATP channels and adenosine receptors.