Neuropeptide Y-family receptors Y₆ and Y₇ in chicken: Cloning, pharmacological characterization, tissue distribution and conserved synteny with human chromosome region

Authors: Bromée, Torun; Sjödin, Paula; Fredriksson, Robert¹; Boswell, Tim²; Larsson, Tomas A.¹; Salaneck, Erik¹; Zoorob, Rima³; Mohell, Nina¹; Larhammar, Dan¹

Source: FEBS Journal, Volume 273, Number 9, May 2006 , pp. 2048-2063(16)

Publisher: Wiley-Blackwell

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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 Y₁, Y₂, Y₄, Y₅ and Y₆, and recently Y₇ has been discovered in fish and amphibians. In chicken we have previously characterized the first four subtypes and here we describe Y₆ and Y₇. The genes for Y₆ and Y₇ are located 1 megabase apart on chromosome 13, which displays conserved synteny with human chromosome 5 that harbours the Y₆ gene. The porcine PYY radioligand bound the chicken Y₆ receptor with a K_d of 0.80 ± 0.36 nm. No functional coupling was demonstrated. The Y₆ mRNA is expressed in hypothalamus, gastrointestinal tract and adipose tissue. Porcine PYY bound chicken Y₇ with a K_d of 0.14 ± 0.01 nm(mean ± SEM), whereas chicken PYY surprisingly had a much lower affinity, with a K_i of 41 nm, perhaps as a result of its additional amino acid at the N terminus. Truncated peptide fragments had greatly reduced affinity for Y₇, in agreement with its closest relative, Y₂, in chicken and fish, but in contrast to Y₂ in mammals. This suggests that in mammals Y₂ has only recently acquired the ability to bind truncated PYY. Chicken Y₇ has a much more restricted tissue distribution than other subtypes and was only detected in adrenal gland. Y₇ seems to have been lost in mammals. The physiological roles of Y₆ and Y₇ 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.

Keywords: G-protein coupled receptor; NPY; paralogon; PYY; synteny

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1742-4658.2006.05221.x

Affiliations: 1: Department of Neuroscience, Unit of Pharmacology, Uppsala University, Sweden 2: Roslin Institute (Edinburgh), Roslin, UK 3: Institut André Lwoff, Unité de Génétique Moléculaire et Intégration des Fonctions Cellulaire, Villejuif, France

Publication date: 2006-05-01