Internalization of pancreatic polypeptide Y4 receptors: correlation of receptor intake and affinity.
Unlike neuropeptide Y receptors, the pancreatic polypeptide Y4 receptors display considerable differences in sequence and ligand-binding affinity across mammalian species. This could produce different receptor turnover rates in the same cellular membrane environment. Comparing rat, human and guinea-pig Y4 receptors expressed in Chinese hamster ovary (CHO) cells (K(d) with human pancreatic polypeptide 14, 45 and 116 pM, respectively), we indeed found human pancreatic polypeptide internalization in the rank order of receptor affinities. A large fraction of the internalized human pancreatic polypeptide, similar across the Y4 species, was associated with secondary endosomes (density approximately 1.05 in Percoll gradients) and lysosomes (density approximately 1.11). For all Y4 receptors examined, this intake was potently and selectively inhibited by cholesterol-complexing polyene antibiotic filipin III and also by clathrin lattice formation inhibitor, phenylarsine oxide. Internalization differences found across Y4 receptor species to a degree compare with those observed for the cloned guinea-pig neuropeptide Y Y1 and human neuropeptide Y Y5 receptors and, generally, support ligand-binding affinities as important determinants of internalization for neuropeptide receptors.
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D010179:Pancreas / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D013045:Species Specificity
D010455:Peptides; D017476:Receptors, Neuropeptide Y; C109491:neuropeptide Y4 receptor