DIFFERENTIAL ACTIONS OF LAMPREY PEPTIDE METHIONINE-TYROSINE AT Y-1 AND Y-2 NEUROPEPTIDE-Y RECEPTORS

Peptide methionine-tyrosine (PMY), a peptide of the neuropeptide Y (NP Y) superfamily isolated from the brain and intestine of the sea lampre y, had the same maximum effect but was 11-fold less potent than pig NP Y in inhibiting field stimulated contraction of the rat vas deferens, an effect mediated through the Y-2 receptor. In contrast, PMY produced a 9-fold greater maximum effect but was 3-fold less potent than pig N PY in contracting the guinea pig mesenteric artery, an effect mediated through the Y-1 receptor. Molecular modelling has suggested that the conformation of PMY is appreciably different from NPY only in the beta -turn region of the molecule (residues 9-14). Our data suggest, theref ore, that modifications in this region of NPY may useful in the design of receptor selective analogs.