Peptide YY derivatives as selective neuropeptide Y/peptide YY Y1 and Y2 agonists devoided of activity for the Y3 receptor sub-type.
Peptide YY derivatives were evaluated for their respective ability to bind and activate the NPY/PYY receptor sub-types (Y1, Y2 and Y3) present in various preparations. The analogue [Leu31,Pro34]PYY demonstrated high (nM) affinity in rat frontoparietal cortical membrane preparations (Y1-enriched tissue) and the rabbit saphenous vein (Y1 in vitro bioassay) but only low affinity in a Y2-enriched preparation (rat hippocampus). In contrast, PYY C-terminal fragments such as PYY3-36 and PYY13-36 were more potent in Y2 than Y1 assays. Interestingly, and in contrast to [Leu31,Pro34]NPY and NPY13-36, the PYY derivatives [Leu31,Pro34]PYY and PYY3-36 were inactive in a purported Y3 bioassay (rat colon). These results suggest that [Leu31,Pro34]PYY and PYY3-36 respectively represent the first selective and potent Y1 and Y2 agonists, devoided of significant affinity/activity for the Y3 receptor class.
Douglas Hospital Research Center, Faculty of Medicine, McGill University, Verdun, Que., Canada.
Y
Y
Dumont
A
A
Cadieux
L H
LH
Pheng
A
A
Fournier
S
S
St-Pierre
R
R
Quirion
D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D002462:Cell Membrane / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000819:agonists*; D019894:Peptide YY; D010455:Peptides / Q000819:agonists / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
D005768:Gastrointestinal Hormones; D009478:Neuropeptide Y; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D019894:Peptide YY