title: Neuropeptide Y as a partial agonist of the Y1 receptor.
abstract: In absence of receptor cycling, human/rat neuropeptide Y was found to persistently occupy the guinea pig neuropeptide Y Y1 receptors expressed on the surface of Chinese hamster ovary (CHO) cells (IC50 approximately 8 nM); a lasting occupancy was also evident with active receptor cycling. A similar blockade was obtained with the human neuropeptide Y Y1 receptor (in CHO or SK-N-MC cells). Peptidic antagonists GR238118 (1229U91) and VD-11 blocked the Y1 receptor in the same molarity range. A neuropeptide Y-related Y1 agonist, (Leu31Pro34) human neuropeptide Y, also strongly adhered to the Y1 site. Similar blockade-like occupancy by neuropeptide Y was found with particulates from Y1-expressing CHO cells, and with native neuropeptide Y Y1 receptors of rat synaptosomes. Peptide YY and a related Y1-selective agonist, (Leu31Pro34) human peptide YY, showed a much less stable binding to the neuropeptide Y Y1 receptor with either the intact cells or particulates. The Y1 binding of neuropeptide Y was also less sensitive to chaotropic agents and guanine nucleotides than the binding of peptide YY, indicating a larger stability for association of neuropeptide Y with the receptor. Inhibition of forskolin-stimulated adenylyl cyclase showed a distinctly attenuating agonism for neuropeptide Y, with an activity similar to peptide YY below 1 nM, but considerably lower above 3 nM of the peptides. This activity was largely exerted via pertussis toxin-sensitive G-proteins of Y1-CHO cells. Our findings indicate that signaling by neuropeptide Y via its Y1 receptor could be self-restricting at higher levels of the peptide, in relation to a strong association of the agonist with the Y1 binding site.
authors.affiliation: Department of Psychiatry, University of Cincinnati School of Medicine, Cincinnati, OH, USA.
authors.forename: Renu
authors.initials: R
authors.lastname: Sah
authors.forename: Ambikaipakan
authors.initials: A
authors.lastname: Balasubramaniam
authors.forename: Michael S
authors.initials: MS
authors.lastname: Parker
authors.forename: Floyd
authors.initials: F
authors.lastname: Sallee
authors.forename: Steven L
authors.initials: SL
authors.lastname: Parker
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D005576:Colforsin; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D019894:Peptide YY / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D019894:Peptide YY; D005576:Colforsin; D000262:Adenylyl Cyclases