Neuropeptide Y‐family receptors Y 6 and Y 7 in chicken

Abstract

The peptides of the neuropeptide Y (NPY) family exert their functions, including regulation of appetite and circadian rhythm, by binding to G‐protein coupled receptors. Mammals have five subtypes, named Y 1 , Y 2 , Y 4 , Y 5 and Y 6 , and recently Y 7 has been discovered in fish and amphibians. In chicken we have previously characterized the first four subtypes and here we describe Y 6 and Y 7 . The genes for Y 6 and Y 7 are located 1 megabase apart on chromosome 13, which displays conserved synteny with human chromosome 5 that harbours the Y 6 gene. The porcine PYY radioligand bound the chicken Y 6 receptor with a K d of 0.80 ± 0.36 n m . No functional coupling was demonstrated. The Y 6 mRNA is expressed in hypothalamus, gastrointestinal tract and adipose tissue. Porcine PYY bound chicken Y 7 with a K d of 0.14 ± 0.01 n m (mean ± SEM), whereas chicken PYY surprisingly had a much lower affinity, with a K i of 41 n m , perhaps as a result of its additional amino acid at the N terminus. Truncated peptide fragments had greatly reduced affinity for Y 7 , in agreement with its closest relative, Y 2 , in chicken and fish, but in contrast to Y 2 in mammals. This suggests that in mammals Y 2 has only recently acquired the ability to bind truncated PYY. Chicken Y 7 has a much more restricted tissue distribution than other subtypes and was only detected in adrenal gland. Y 7 seems to have been lost in mammals. The physiological roles of Y 6 and Y 7 remain to be identified, but our phylogenetic and chromosomal analyses support the ancient origin of these Y receptor genes by chromosome duplications in an early (pregnathostome) vertebrate ancestor.