Pharmacological characterization of cloned chicken neuropeptide Y receptors Y(1) and Y(5).

摘要

The neuropeptide Y (NPY) receptor subtypes Y(1) and Y(5) are involved in the regulation of feeding and several other physiological functions in mammals. To increase our understanding of the origin and mechanisms of the complex NPY system, we report here the cloning and pharmacological characterization of receptors Y(1) and Y(5) in the first non-mammal, chicken (Gallus gallus). The receptors display 80-83% and 64-72% amino acid sequence identity, respectively, with their mammalian orthologues. The three endogenous ligands NPY, peptide YY (PYY) and pancreatic polypeptide (PP) have similar affinities as in mammals, i.e. NPY and PYY have subnanomolar affinity for both receptors whereas chicken PP bound with nanomolar affinity to Y(5) but not to Y(1). A notable difference to mammalian receptor subtypes is that the Y(1) antagonist SR120819A does not bind chicken Y(1), whereas BIBP3226 does. The Y(5) antagonist CGP71863A binds to the chicken Y(5) receptor. Anatomically, both Y(1) and Y(5) have high mRNA expression levels in the infundibular nucleus which is the homologous structure of the hypothalamic arcuate nucleus in mammals. These results suggest that some of the selective Y(1) and Y(5) antagonists developed in mammals can be used to study appetite regulation in chicken.