[3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain.

摘要: Characterization of the adenosine A2 receptor has been limited due to lack available ligands which have high affinity and selectivity for this subtype. In present study, binding a highly A2-selective agonist radioligand, [3H]CGS 21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine) is described. specific rat striatal membranes was saturable, reversible dependent upon protein concentration. Saturation studies revealed that bound with (Kd = 15.5 nM) capacity (apparent Bmax 375 fmol/mg protein) single class recognition sites. Estimates ligand (16 determined from association dissociation kinetic experiments were in close agreement results saturation studies. greatest negligible obtained cortical membranes. Adenosine agonists competed 5 nM following order activity; CGS 5'-N-ethylcarboxamidoadenosine greater than 2-phenylaminoadenosine (CV-1808) 5'-N-methylcarboxamidoadenosine 2-chloroadenosine R-phenylisopropyladenosine N6-cyclohexyladenosine N6cyclopentyltheophylline S-phenylisopropyladenosine. The nonxanthine antagonist, 15943A, most active compound inhibiting 21680. Other antagonists inhibited order; xanthine amine congener (1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine 1,3-dipropyl-8-cyclopentylxanthine 1,3-diethyl-8-phenylxanthine 8-phenyltheophylline 8-cyclopentyltheophylline carboxylic acid 8-parasulfophenyltheophylline theophylline caffeine. pharmacological profile both antagonist compounds compete consistent selective interaction at receptor. A positive correlation (r 0.98, P less .01) observed between inhibit [3H]NECA (+50 CPA) receptors. However, some differences these assays found moderate nonselective actions A1 subtypes. Unlike data ligands, indicate directly labels brain without need block activity receptor.(ABSTRACT TRUNCATED AT 400 WORDS)