Apparent affinity and potency of BIBP3226, a non-peptide neuropeptide Y receptor antagonist, on purported neuropeptide Y Y1, Y2 and Y3 receptors.
The newly developed, purported non-peptide neuropeptide Y Y1 receptor antagonist BIBP3226 was evaluated for its potential effect on the recently characterized Y3 receptor subtype and for its apparent affinity in rat and human brain membrane binding assays using highly selective neuropeptide Y Y1 and Y2 radioligands. BIBP3226 potently blocked (pA2 = 7.36) the contractile effect of neuropeptide Y in the rabbit saphenous vein, a Y1 receptor bioassay and demonstrated nM affinity for Y1/[125I][Leu31,Pro34]peptide YY binding sites. In contrast, it failed to antagonize the biological effects of neuropeptide Y in the rat vas deferens (Y2) and rat colon (Y3) and did not significantly competed for Y2/[125I]peptide YY-(3-36) binding sites in rat and human brain homogenates. Taken together, the results demonstrate further the high potency and selectivity of BIBP3226 for the neuropeptide Y Y1 receptor by establishing its lack of antagonist activity on the Y3 subtype.
Jacques
D
D
Douglas Hospital Research Centre, Faculty of Medicine, McGill University, Verdun, Québec, Canada.
Cadieux
A
A
Dumont
Y
Y
Quirion
R
R
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005768:Gastrointestinal Hormones / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019894:Peptide YY; D010455:Peptides / Q000037:antagonists & inhibitors*; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000145:classification; D012501:Saphenous Vein / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
C092926:BIBP 3226; D005768:Gastrointestinal Hormones; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; D001120:Arginine