Characterization of the Binding Sites of [3H]SR 48968, a Potent Nonpeptide Radioligand Antagonist of the Neurokinin-2 Receptor

Abstract [ 3 H]SR 48968, a radiolabeled nonpeptide antagonist of NK-2 receptor, has been tested in ligand-receptor binding assays using rat duodenum, hamster urinary bladder and guinea pig ileum membranes. [ 3 H]SR 48968 bound to a single class of high affinity binding sites. Its affinity was slightly species-dependent. Its binding was inhibited by neurokinins, following the rank order of potency NKA > NKB > SP. It was also inhibited by peptide antagonists of NK-2 receptor (MEN 10,376, L 659,877), but their relative potencies were highly species-dependent. Unlabeled SR 48968, but not its R-enantiomer (SR 48965), also potently inhibited its binding. These data show that [ 3 H]SR 48968 potently binds to NK-2 receptor and therefore is a useful tool to study NK-2 receptor.