Alpha 2-agonist binding sites in brain: [125I]para-iodoclonidine versus [3H]para-aminoclonidine

The localization of alpha 2-receptors was determined by quantitative autoradiography using [125I]para-iodoclonidine ([125I]PIC) and [3H]para-aminoclonidine ([3H]PAC). In cortical tissue, [125I]PIC and [3H]PAC were equipotent in their capacity to bind sites recognized by oxymetazoline (preferentially binds to the alpha 2A receptor subtype). The iodinated ligand was about 10 times more potent than [3H]PAC for binding to the heterogenous receptor population labeled by ARC-239 (alpha 2B and alpha 2C). The density of [125I]PIC binding was found to be two-fold higher than that of [3H]PAC in many brain areas and the disparity was even greater in regions such as the dentate gyrus, stria terminalis, and granular layer of the cerebellum. By contrast, other regions of the brain such as the laterodorsal thalamic nucleus, the locus coeruleus, and several amygdaloid areas had equivalent levels of binding. These observations indicate that [3H]PAC has selectivity for the alpha 2A receptor subtype and thus offer a restricted view of alpha 2-adrenergic receptor distribution. The iodinated ligand provides a more complete picture of the overall alpha 2 receptor population.