Differential actions of lamprey peptide methionine-tyrosine at Y₁ and Y₂ neuropeptide Y receptors

Peptide methionine-tyrosine (PMY), a peptide of the neuropeptide Y (NPY) superfamily isolated from the brain and intestine of the sea lamprey, had the same maximum effect but was 11-fold less potent than pig NPY in inhibiting field-stimulated contraction of the rat vas deferens, an effect mediated through the Y₂ receptor. In contrast, PMY produced a 9-fold greater maximum effect but was 3-fold less potent than pig NPY in contracting the guinea pig mesenteric artery, an effect mediated through the Y₁ receptor. Molecular modelling has suggested that the conformation of PMY is appreciably different from NPY only in the β-turn region of the molecule (residues 9-14). Our data suggest, therefore, that modifications in this region of NPY may useful in the design of receptor selective analogs.