Binding of chimeric NPY/galanin peptides M32 and M242 to cloned neuropeptide Y receptor subtypes Y1, Y2, Y4, and Y5

Ligand binding to neuropeptide Y (NPY) receptors Y1, Y2, Y4, and Y5 from gu inea-pig was investigated using the two NPY-galanin hybrids M32 (galanin1-1 3-NPY25-36-amide) and M242 ([D-Trp(32)]M32). The affinity of M32 for Y1, Y2 , and Y4 receptors was 13, 4, and 30 nM, respectively, similar to that of N PY18-36 and NPY22-36 but 40-fold to 300-fold lower than the affinity of int act porcine NPY. M242 bound to the Y1, Y2, and Y4 receptors with 9-fold to 20-fold lower affinity than did M32. The affinities of M32 and M242 for Y5 were 400 and 800 nM, respectively. Thus, M32 seems to gain affinity relativ e to both of its constituent peptide portions although the NPY25-36 part ma y be sufficient for NPY-receptor recognition, especially at the Y2 receptor . This suggests that the galanin portion of M32 influences and/or stabilize s the conformation of the NPY portion, similar to the effect seen for the N PY portion of M32 in binding to galanin receptors. (C) 2001 Harcourt Publis hers Ltd.