Binding of adrenergic ligands ([3H]clonidine and [3H]WB-4101) to multiple sites in human brain

Abstract In order to identify alpha-adrenoceptors in post-mortem human brain and to detect the possible existence of multiple types of binding sites for adrenergic [ 3 H]ligands, we studied the binding of [ 3 H]clonidine and [ 3 H]WB-4101 to human brain cerebral cortex, hippocampus, hypothalamus and striatum. Frontal cortex revealed two binding sites for [ 3 H]clonidine (with K D values of approximately 1 and 8 nM), as indicated by the biphasic Scatchard plot, the biphasic pattern of dissociation kinetics, and the biphasic inhibition by phentolamine on the binding of [ 3 H]clonidine; the high-affinity site was heat-labile. Two high-affinity binding sites for [ 3 H]WB-4101 were also detected in the human frontal cortex (with K D values of about 0.09 and 1.5 nM), as revealed by a biphasic pattern of dissociation. A third site with low affinity binding for [ 3 H]WB-4101 was detected by the biphasic inhibition by phentolamine (as well as by WB-4101 and prazosin) on the binding of [ 3 H]WB-4101. The three other brain regions revealed very similar patterns exhibited by the frontal cortex, except that the density of the [ 3 H]clonidine sites (of either high or low affinity) was highest in the hypothalamus, whereas the density of [ 3 H]WB-4101 sites was highest in the hippocampus.