Regional Distribution of α2A‐and α2B‐Adrenoceptor Subtypes in Postmortem Human Brain

Abstract: The newly available and highly selective radiolabeled antagonist [3H]RX 821002 was used to examine the distribution of α2 adrenoceptors in human brain. High densities of α2 adrenoceptors were found in the hippocampus, frontal cortex, thalamus, amygdala, pons, and medulla oblongata. Intermediate densities were observed in the striatum (nucleus accumbens, nucleus caudatus, and putamen), globus pallidus, and substantia nigra. The KD values for [3H]RX 821002 were similar in all regions (ranging from 2.8 to 7.5 nM). On the basis of their different affinities for prazosin and oxymetazoline, the α2 adrenoceptors have been divided into α2A and α2B subtypes. To examine the α2A/α2B‐adrenoreceptor ratio in the different brain regions, we performed oxymetazoline and prazosin/[3H]RX 821002 competition binding experiments. In frontal cortex membranes, the competition curves with prazosin were steep, indicating a single class of binding sites, whereas the competition curves with oxymetazoline were shallow and fitted by computer best to a two‐site model. However, in the presence of GTP, the high‐affinity sites for oxymetazoline were partially converted into low‐affinity sites, indicating that this agonist interacts with high‐ and low‐affinity states of the α2 adrenoceptors. This implies that oxymetazoline is not very suitable for discriminating the α2A‐and α2B‐receptor subtypes in radioligand binding studies. Therefore, prazosin/[3H]RX 821002 competition binding experiments were used to investigate the distribution of the α2‐adrenoceptor subtypes in human brain. The α2A‐receptor subtype was detected in all brain regions examined. In contrast, α2B receptors were only observed in striatum and globus pallidus.