Visualization of neurokinin-3 receptor sites in rat brain using the highly selective ligand [ 3H]senktide

The autoradiographic distribution of the neurokinin (NK)-3 receptor sub-type was visualized in the rat brain using [ 3H]senktide, a highly selective ligand. [ 3H]Senktide apparently binds to a single class of high affinity ( K d = 2.8 ± 1.0nM), low capacity ( B max = 31.2 ± 3.0fmol/mg protein) sites in rat brain cortex. The ligand selectivity pattern reveals that eledoisin and senktide are potent competitors of both [ 3H]senktide and [ 125I]Bolton-Hunter eledoisin binding sites demonstrating the NK-3 nature of these sites. Autoradiographic data show that [ 3H]senktide binding sites are concentrated in mid-cortical layers, supraoptic nucleus, zona incerta, basolateral nucleus of the amygdala and interpeduncular nucleus. Much lower densities of binding are seen in most other areas such as the caudate-putamen and cerebellum. This distribution is similar, but not identical, to that previously reported for NK-3 sites using less selective ligands. It is most likely because less selective probes also bind to other classes of NK receptors. The higher selectivity of [ 3H]senktide is thus an important advantage for the precise characterization of NK-3 receptor binding parameters.