Autoradiographic distribution of brain neurokinin-1/substance P receptors using a highly selective ligand [ 3H]-[Sar 9,Met(O 2) 11]-substance P

The autoradiographic distribution of neurokinin (NK)-1 receptors was visualized in the rat brain using the highly selective ligand, [ 3H]-[Sar 9,Met(O 2) 11]-substance P. This ligand apparently binds to a single class of high affinity ( K d = 1.4 ± 0.5nM ), low capacity ( B max= 160 ± 3.0fmol/mg protein) sites in rat brain membrane preparations. The ligand selectivity profile reveals that substance P (SP) and unlabeled [Sar 9,Met(O 2) 11]-SP are potent competitors of [ 3H]-[Sar 9,Met(O 2) 11]-SP binding while NK-2 and NK-3 analogues are virtually inactive demonstrating the selectivity of this radioligand for the NK-1 receptor class. Autoradiographic data show that [ 3H]-[Sar 9,Met(O 2) 11]-SP binding sites are broadly but discretely distributed in rat brain, the highest densities of sites being located in the external plexiform layer of the olfactory bulb, striatum, olfactory tubercule, amygdala-hippocampal area, endopiriform and entorhinal cortices, superior colliculus, locus coeruleus and substantia gelatinosa of the spinal cord. This distribution is similar, but not identical, to that previously reported for NK-1 sites using less selective ligands such as [ 125I]Bolton-Hunter SP. For example, some difference in labelling patterns are observed in the hippocampal formation. This could be explained by the existence of NK-1 receptor subtypes, only one of them being recognized by [ 3H]-[Sar 9,Met(O 2) 11]-SP or by the greater selectivity of this radioligand for NK-1 over NK-2 and NK-3 receptor classes.