Modulation of A2A 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 A2A-receptor selective agonist [3H]CGS 21680. Radioligand binding studies in bovine brain striatal membranes (BBM) indicated that unlabeled CGS 21680 displaced the bound [3H]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 [3H]CGS 21860 by approximately 28% at 10(-4) M. [3H]CGS 21680 bound to BBM in a saturable manner to a single binding site (Kd = 10.6+/-1.71 nM; Bmax = 221.4+/-6.43 fmol/mg of protein). In contrast, [3H]CGS 21680 showed saturable binding to two sites in the presence of 10(-5) M glibenclamide; (Kd = 1.3+/-0.22 nM; Bmax = 74.3+/-2.14 fmol/mg protein; and Kd = 8.9+/-0.64 nM; Bmax = 243.2+/-5.71 fmol/mg protein), indicating modulation of adenosine A2A receptors by glibenclamide. These studies suggest that the K+(ATP) channel blocker, glibenclamide, modulated the adenosine A2A receptor in such a manner that [3H]CGS 21680 alone recognizes a single affinity adenosine receptor, but that the interactions between K+(ATP) channels and adenosine receptors.
Olanrewaju
H A
HA
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Marala
R B
RB
Mustafa
S J
SJ
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism* / Q000648:ultrastructure; D005905:Glyburide / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction
D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D005905:Glyburide