Distribution of adenosine receptors in the postmortem human brain: an extended autoradiographic study.

Whole-hemisphere sections from six subjects were used in a quantitative autoradiographic study to characterize and to investigate the distribution of adenosine receptors, using [3H]DPCPX, [3H]CGS 21680, and [3H]SCH 58261 as radioligands. [3H]DPCPX-binding showed the pharmacology expected for adenosine A1 receptors and is therefore taken to mirror adenosine A1 receptors. Adenosine A1 receptors were widely distributed, with the highest densities in the stratum radiatum/pyramidale of the hippocampal region CA1. Adenosine A1 receptors were nonhomogeneously distributed in nucleus caudatus, globus pallidus, and cortical 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 A1 receptors in structures known to be important for cholinergic transmission, especially the septal nuclei. The Bmax values and KD values for [3H]DPCPX-binding in stratum 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, respectively. [3H]CGS 21680-binding was multiphasic, but showed the pharmacology expected for adenosine A2A receptors and was taken to represent them. Adenosine A2A receptors were abundant in putamen, nucleus caudatus, nucleus accumbens, and globus pallidus pars lateralis. Specific [3H]CGS 21680-binding was also found in certain thalamic nuclei and throughout the cerebral cortex. The adenosine A2A receptor antagonist radioligand [3H]SCH 58261 was also found to label these extrastriatal structures. Thus, adenosine A2A receptors seem to be more widely distributed in the human brain than previously recognized.