Characterization of the Cloned Atlantic Cod Neuropeptide Y-Yb Receptor: Peptide-Binding Requirements Distinct from Known Mammalian Y Receptors

Abstract

Five members of the neuropeptide Y (NPY) receptor family have been cloned in mammals. The recently cloned NPY receptor in the Atlantic cod seems to be distinct from the mammalian subtypes as it has only 50% identity to Y1, Y4, and y6 and only 30% to Y2 and Y5. In most of the other families of G-protein-coupled receptors, species homologues have 65–90% identity between fishes and mammals. The functional expression and detailed pharmacological characterization of this cod NPY receptor, designated Yb, is reported. Membranes of cells transiently transfected with cod Yb showed saturable [125I]PYY binding with a Kd of 45 pM. The pharmacological profile is similar to those of both the zebrafish Yb and Yc receptors and distinct from those of the mammalian NPY receptors. In competition experiments the cod Yb receptor had the following rank order of potencies: porcine PYY = porcine NPY = p[Leu31, Pro34]NPY > zebrafish PYY > zebrafish NPY >> NPY2-36 = NPY3-36 > NPY18-36 > bovine PP = [D-Trp32]NPY > BIBP3226. This is in sharp contrast to the high selectivity of BIBP3226 for the Y1 receptor from all mammalian species. Together with the low amino acid identity of cod Yb with the mammalian Y1, Y4, and y6 receptors, this is further support for the notion that fish Yb constitutes a distinct NPY receptor subtype.