CHARACTERIZATION OF [I-125] [MEPHE(7)]NEUROKININ-B BINDING TO TACHYKININ NK3 RECEPTORS - EVIDENCE FOR INTERSPECIES VARIANCE

Human tachykinin NK3 receptors expressed in Chinese hamster ovary (CHO-K1) cells were characterised using the novel radioligand [I-125]iodohistidyl,[MePhe(7)]neurokinin B ([I-125][MePhe(7)]neurokinin B). [I-125][MePhe(7)]neurokinin B was shown to label human NK3 binding sites with high affinity in a saturable and reversible manner. The rank order of affinity of a range of tachykinin ligands confirmed that the tachykinin receptor expressed was the NK3 receptor type. An interspecies comparison of NK3 binding sites revealed pharmacological differences between human, guinea pig and rat tachykinin NK3 receptors. The NK2 selective antagonist SR 48968, inhibited binding of [I-125][MePhe(7)]neurokinin B to NK3 binding sites with K-i values of 287 nM and 205 nM in human and guinea pig respectively, but was > 30-fold less active in the rat.