[ 125 I]Leu 31 , Pro 34 -PYY is a High Affinity Radioligand for Rat PP1/Y4 and Y1 Receptors: Evidence for Heterogeneity in Pancreatic Polypeptide Receptors

Y4 Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

“…The order of potency for hY 4 cells (hPP Ն rPP Ͼ GR231118 Ͼ PYY Ն Pro 34 PYY) was the same as that described for hY 4 receptors in CHO membranes Eriksson et al, 1998). Relative peptide affinities at the mY 4 receptor (rPP Ն hPP Ͼ GR231118 Ն Pro 34 PYY Ͼ Ͼ PYY) resemble those described for the rY 4 receptor (Gehlert et al, 1997;Eriksson et al, 1998).…”

“…The Gehlert et al, 1996Gehlert et al, , 1997Matthews et al, 1997;Eriksson et al, 1998;Schober et al, 2000). We used […”

Evidence for the Existence of an Additional Class of Neuropeptide Y Receptor Sites in Rat Brain

“…However, under these assay conditions, the possible recognition of the Y 4 subtype could not be fully excluded because [Leu 31 ,Pro 34 ]PYY is known to possess nanomolar affinity for this receptor (Gehlert et al, 1996). It is interesting that, using purported Y 4 ligands such as 125 I-hPP, 125 I-rPP, and 125 I-labeled bovine PP, we were able to visualize a very discrete distribution of specific receptor sites with moderate to very high amounts seen in a few regions, including the medial preoptic area, paraventricular nucleus of the hypothalamus, and interpeduncular nucleus (Trinh et al, 1996;Gehlert et al, 1997). Furthermore, quantitative receptor autoradiography has demonstrated that labeling seen with 125 I-rPP (a Y 4 ligand with low affinity for the Y 5 receptor) was not identical to that of specific 125 I-hPP.…”

“…Furthermore, quantitative receptor autoradiography has demonstrated that labeling seen with 125 I-rPP (a Y 4 ligand with low affinity for the Y 5 receptor) was not identical to that of specific 125 I-hPP. In some rat brain nuclei such as the interpeduncular nuclei, nucleus tractus solitarius, and area postrema, higher levels of specific 125 I-hPP binding sites were detected compared with specific 125 I-rPP binding (Trinh et al, 1996) (Gehlert et al, 1997) and 125 I-GR231118 (Dumont and Quirion, 2000;Schober et al, 2000) binding sites even if these two radioligands are known to possess high affinities for the Y 4 receptor subtype (Dumont et al, 2004a). These results could be taken as evidence for the existence of yet another class of sites preferentially recognized by PPrelated molecules.…”

Pancreatic Polypeptide Is Recognized by Two Hydrophobic Domains of the Human Y4 Receptor Binding Pocket

“…4 R-A set of NMR structure conformations of bovine pancreatic polypeptide (PDB code 1LJV) (44) was docked into the hY 4 R comparative models. Bovine pancreatic polypeptide differs only on positions 6 and 23 with respect to hPP and has similar affinity for the hY 4 R as earlier reported (45,46). The use of ILJV provided a guide for the structural distinction between the peptide's helical region and dynamic tail region.…”