title: The binding of the adenosine A2 receptor selective agonist [3H]CGS 21680 to rat cortex differs from its binding to rat striatum.
abstract: The binding of the reportedly A2A selective agonist CGS 21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'N-ethylcarboxamidoadenos ine) to cortex and striatum was examined in parallel using quantitative receptor autoradiography. [3H]CGS 21680 bound to a single site in rat striatum with KD 2.3 nM and Bmax 320 fmol/mg grey matter. In addition [3H]CGS 21680 bound to a single site in the cerebral cortex with KD 47 nM and Bmax 100 fmol/mg grey matter. In cat cortex [3H]CGS 21680 (2 nM) binding was strong and particularly evident in the most superficial layers. The potency order for inhibition of 2 nM [3H]CGS 21680 binding to rat striatum was NECA (5'-N-ethylcarboxamidoadenosine; IC50 9.0 nM) > 2-CADO (2-chloroadenosine; 87 nM) > R-PIA (N6-(R)-phenylisopropyladenosine; 110 nM). The potency order for inhibition of 2 nM [3H]CGS 21680 binding to rat cortex was NECA (3.0 nM) > 2-CADO (14 nM) > or = R-PIA (16 nM). Gpp(NH)p (5'-guanylyl imidodiphosphate) inhibited [3H]CGS 21680 binding to both cortex and striatum, but more potently in cortex (IC50 100 nM vs. 470 nM). The present results show that there is a cortical binding site for [3H]CGS 21680 which appears to be different from the the striatal A2A receptor, the A2B receptor and the A1 receptor.
authors.affiliation: Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Johansson
authors.forename: V
authors.initials: V
authors.lastname: Georgiev
authors.forename: F E
authors.initials: FE
authors.lastname: Parkinson
authors.forename: B B
authors.initials: BB
authors.lastname: Fredholm
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002415:Cats; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D010627:Phenethylamines / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*
chemical_list: D010627:Phenethylamines; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D006165:Guanylyl Imidodiphosphate; D000241:Adenosine