title: Effects of the neuropeptide Y (NPY)-receptor antagonist BIBP3226 on vascular NPY-receptors with different ligand requirements.
abstract: The aim was to examine effects of a newly developed neuropeptide Y (NPY)-receptor antagonist, BIBP3226 and to characterize NPY-receptors in the isolated guinea pig caval vein and human subcutaneous artery, respectively. BIBP3226 < or = 1 microM did not affect the basal tension. Pretreatment with increasing concentrations of BIBP3226 (10 nM-1 microM) resulted in a progressive rightward shift of the concentration-response curve to the Y1-receptor selective agonist [Pro34]NPY in the guinea pig caval vein. Regression analysis of the Schild plot gave a pA2-value of 7.58 (7.20-8.33, 95% confidence interval), slope of regression line 0.96 (0.52-1.39, 95% confidence interval) and a correlation coefficient of 0.78. NPY and the C-terminal NPY 2-36 evoked equipotent concentration-dependent contractions, both of which were sensitive to BIBP3226. Although less potent than NPY 2-36, also the contraction induced by NPY 5-36 was antagonized by BIBP3226. In the human subcutaneous artery [Pro34]NPY but not NPY 2-36 (< or = 0.3 microM) evoked a concentration-dependent contraction. Pretreatment with BIBP3226 (0.1 microM) resulted in a rightward shift of the concentration-response curve to [Pro34]NPY (from 7.38 +/- 0.10 to 6.95 +/- 0.16 (P < 0.05, n = 6). The present study has shown that the Y1-receptor-selective antagonist BIBP3226 potently antagonizes vascular NPY-receptors with different ligand requirements in the guinea pig caval vein and human subcutaneous artery, respectively. It appears that the guinea pig Y1-receptor is much less stringent in its demand on the N-terminal part of NPY than that of human Y1-receptors.
authors.affiliation: Department of Clinical Pharmacology, Lund University Hospital, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Grundemar
authors.forename: M
authors.initials: M
authors.lastname: Ekelund
mesh_terms: D000009:Abdominal Muscles / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014682:Vena Cava, Inferior / Q000187:drug effects / Q000378:metabolism
chemical_list: C092926:BIBP 3226; D008024:Ligands; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D001120:Arginine