BIBP3226 INHIBITS NEUROPEPTIDE-Y AND PANCREATIC-POLYPEPTIDE POTENTIATED NEUROGENIC VASOCONSTRICTION

Neuropeptide Y (NPY) potentiates the contractile response of the rat c audal artery to adrenergic nerve stimulation in-vitro. The NPY Y-1 sel ective antagonist BIBP3226 acetyl)-N-[(4-hydroxyphenyl)methyl]-arginin amide), inhibited the vascular effects of NPY in rat caudal artery pre parations in-vitro (IC50 =126 nM). BIBP3226 also inhibited the effects of the selective Y-1 agonist [Leu(31),Pro(34)]NPY and completely abol ished the effects of avian pancreatic polypeptide that was shown to be capable of potentiating neurogenic vasoconstriction in this preparati on. These effects were reversible and are most likely mediated by the Y-1 receptor subtype since we failed to observe any functional evidenc e of a Y-2 receptor subtype in rat caudal artery. The caudal artery pr ovides a useful functional assay for pharmacological analysis of NPY a nd NPY antagonists.