CLONING AND FUNCTIONAL EXPRESSION OF THE GUINEA-PIG NEUROPEPTIDE-Y Y2RECEPTOR

Five neuropeptide Y (NPY) receptor subtypes have been cloned in mammal s. The degree of sequence conservation differs considerably between su btypes as well as between evolutionary lineages. To shed further light on this, we have cloned the five NPY receptors in the guinea pig. Her e, we report the cloning of the guinea pig Y2 receptor. The Y2 recepto r is generally highly conserved, with 90-95% identity between differen t orders of mammals, including the guinea pig. The guinea pig receptor has a divergent cytoplasmic tail, indicating possible differences in regulation of signalling and/or down regulation. COS-7 cells transient ly transfected with the gpY2 receptor show saturable I-125-PYY binding with a K-d = 6 pM. In displacement experiments, the gpY2 receptor was similar to the human and rat receptors with the following rank order of potencies: pNPY >pPYY>pNPY13-36 = pNPY22-36 much greater than [Leu( 31)Pro(34)]NPY>BIBP3226. Thus, the guinea pig Y2 receptor is well cons erved in comparison with human and rat with regard to both amino acid sequence and pharmacological profile. (C) 1998 Elsevier Science B.V. A ll rights reserved.