DISTRIBUTION OF ADENOSINE RECEPTORS IN THE POSTMORTEM HUMAN BRAIN - AN EXTENDED AUTORADIOGRAPHIC STUDY

Whole-hemisphere sections from six subjects were used in a quantitativ e autoradiographic study to characterize and to investigate the distri bution of adenosine receptors, using [H-3]DPCPX, [H-3]CGS 21680, and [ H-3]SCH 58261 as radioligands. [H-3]DPCPX-binding showed the pharmacol ogy expected for adenosine A(1) receptors and is therefore taken to mi rror adenosine A(1) receptors. Adenosine A(1) receptors were widely di stributed, with the highest densities in the stratum radiatum/pyramida le of the hippocampal region CA1. Adenosine A(1) receptors were nonhom ogeneously distributed in nucleus caudatus, globus pallidus, and corti cal areas: In the cingulate and frontal cortex the deep layers showed the highest labeling, while in the occipital, parietal, temporal, and insular cortex it was highest in the superficial layers. In addition, we found very high levels of adenosine A(1) receptors in structures kn own to be important for cholinergic transmission, especially the septa l nuclei. The B-max values and K-D values for [H-3]DPCPX-binding in st ratum radiatum/pyramidale of CA1 and the superficial layer of insular cortex were 598 and 430 fmol/mg gray matter and 9.9 and 14.2 nM, respe ctively. [H-3] CGS 21680-binding was multiphasic, but showed the pharm acology expected for adenosine A(2A) receptors and was taken to repres ent them. Adenosine A(2A) receptors were abundant in putamen, nucleus caudatus, nucleus accumbens, and globus pallidus pars lateralis. Speci fic [3H]CGS 21680-binding was also found in certain thalamic nuclei an d throughout the cerebral cortex. The adenosine A(2A) receptor antagon ist radioligand [H-3]SCH 58261 was also found to label these extrastri atal structures. Thus, adenosine A(2A) receptors seem to be more widel y distributed in the human brain than previously recognized.