Cloning and characterization of rhesus monkey neuropeptide Y receptor subtypes

Neuropeptide Y (NPY) is a 36 amino acid peptide that is abundant in the bra in and peripheral nervous system. NPY has a variety of effects when adminis tered into the brain including a pronounced feeding effect, anxiolysis, reg ulation of neuroendocrine axes and inhibition of neurotransmitter release. These effects are mediated by up to 6 G protein coupled receptors designate d Y1, Y2, Y3, Y4, Y5 and y6. To better understand the phylogeny and pharmac ology of NPY in non-human primates, we have cloned and expressed the NPY Y1 , Y2 and Y5 receptor subtypes from the rhesus monkey. No cDNA sequence enco ding a Y l receptor was found suggesting substantial sequence differences w hen compared to the human sequence. Comparison of these sequences with thos e from human indicated strong sequence conservation of Y1. Y2 and Y5 betwee n the two species. The displacement of I-125-PYY binding to the rhesus monk ey and human receptors by various peptides was compared to evaluate the pha rmacology of the two species. Similar pharmacologies were noted across the species at the various receptor subtypes. These results indicate the rhesus monkey and human NPY receptor subtypes have a close amino acid sequence co nservation and that the peptide recognition domains are conserved as well. (C) 2001 Elsevier Science Inc. All rights reserved.