Autoradiographic characterization of high-affinity adenosine A2 receptors in the rat brain.

Binding of the non-selective adenosine receptor agonist, [3H]NECA (5'-N-ethylcarboxamidoadenosine) was evaluated in sections of rat brain using quantitative receptor autoradiography. [3H]NECA bound specifically to a variety of different brain regions including striatum, cerebellum and thalamus. In the presence of the selective adenosine A1 receptor agonist, cyclopentyladenosine (CPA: 50 nM), [3H]NECA binding was exclusively localized to the striatum and olfactory tubercle. Binding in rat striatum occurred at a single site (Kd = 9 nM) with limited capacity (apparent Bmax = 230 fmol/mg tissue). Competition experiments in both striatum and olfactory tubercle with various adenosine agonists and antagonists indicated that the sites labeled by [3H]NECA in the presence of 50 nM CPA were A2 in nature, the rank order of activity for agonists being NECA greater than 2-chloroadenosine (2-CADO), greater than R-N6-phenylisopropyladenosine (R-PIA) greater than CPA greater than S-N6-phenylisopropyladenosine (S-PIA). For xanthine antagonists the order was greater than 1,3-dipropyl-8(2-amino-4-chloro)phenylxanthine (PACPX) greater than xanthine amino acid congener (XAC) greater than xanthine carboxylic acid congener (XCC) greater than 1,3-diethyl-8-phenylxanthine (DPX). The localization of A2 receptors to discrete regions of rat brain indicates that the purine may have a selective role in modulating basal ganglia function.