Mapping Peptide-binding Domains of the Substance P (NK-1) Receptor from P388D Cells with Photolabile Agonists

The tachykinin substance P (SP) is a peptide transmitter of primary afferents. Its actions on both central and peripheral targets are mediated by a G-protein-coupled receptor of known primary structure. To identify contact sites between the undecapeptide SP and its receptor, we prepared radiolabeled photoreactive analogs of SP (H-RPKPQQFFGLM-NH 2 ) by replacing amino acids in the peptide with p -benzoyl-L-phenylalanine (BPA). SP, BPA 3 -SP, and BPA 8 -SP bind with high affinity ( K