Adenosine receptors in post-mortem human cerebral cortex and the effect of carbamazepine

Representative A1 site- and A2 site-selective ligands for adenosine receptors were found to bind to a single class of non-co-operative sites in synaptic membranes prepared from pieces of normal human temporal lobe cerebral cortex obtained at autopsies performed within 24 h post-mortem. The known adenosine antagonists theophylline and 1-isobutyl-3-methylxanthine also bound to these sites and could completely displace either ligand. Computer analysis combining data from 21 separate experiments which used membranes prepared from seven different autopsy cases gave the following kinetic parameters for the site: equilibrium dissociation constants (KD) for L-PIA, 4.1 +/- 0.9 nmol/l; KD for NECA, 26 +/- 4 nmol/l; KD for theophylline, 28 +/- 5 mumol/l; receptor number (Bmax), 510 +/- 77 fmol/mg protein. Carbamazepine could also displace either radioligand from the sites, although solubility limits for this drug were reached at 50% receptor occupancy. The KD for carbamazepine was 138 +/- 18 mumol/l. Other anticonvulsants tested were generally ineffective at their therapeutic concentrations, although phenytoin showed a small amount of ligand binding inhibition. The results are in line with earlier studies in rodent tissue preparations, and suggest a possible purinergic component in the anticonvulsant activity of carbamazepine in a man.