<p>Neuropeptide Y (NPY) is an abundant neurotransmitter in the nervous system and forms a family of evolutionarily related peptides together with peptide YY (PYY), pancreatic polypeptide (PP) and polypeptide Y (PY). These peptides are ligands to a family of receptors that mediate a wide range of physiological effects including stimulation of appetite. This work describes the molecular cloning of four novel NPY receptors.</p><p>In rat a receptor called PP1, later renamed Y<sub>4</sub>, was cloned and characterized. It displays the highest amino acid sequence identity to the Y<sub>1</sub> receptor. Rat Y<sub>4</sub> differs extensively from human Y<sub>4</sub>, cloned subsequently, in both pharmacological properties, tissue distribution, and amino acid sequence with only 75% identity. Rat and human Y<sub>4 </sub>are the most diverged orthologues in the NPY receptor family.</p><p>In guinea pig, the y<sub>6</sub> receptor gene was found to be a pseudogene with several frameshift mutations. The gene is a pseudogene in human and pig too, but seems to give rise to a functional receptor in mouse and rabbit. This unusual evolutionary situa- tion may be due to inactivation of the gene in a mammalian ancestor and then restoration of expression in mouse and rabbit, but perhaps more likely due to independent inactivations in guinea pig, human and pig.</p><p>In zebrafish, two new intronless receptor genes were cloned. Sequence comparisons suggest that both receptors are distinct from the mammalian receptors Y<sub>1</sub>, Y<sub>4</sub> and y<sub>6</sub>, hence they were named Ya and Yb. Chromosomal localization provides further support that Ya and Yb may be distinct subtypes. </p><p>The discoveries of the rat Y<sub>4</sub> and zebrafish Ya and Yb receptors were unexpected and show that the NPY receptor family is larger than previously thought.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-496 |
| Date | January 2000 |
| Creators | Starbäck, Paula |
| Publisher | Uppsala University, Department of Neuroscience, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 948 |
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