The dog saphenous vein: A sensitive and selective preparation for the Y-2 receptor of neuropeptide Y

The dog saphenous vein responds to neuropeptide Y with a dose-dependent contraction and this vasopressor effect is not altered by the removal of the endothelium nor by the neuropeptide Y Y-1 receptor antagonist, BIBP 3226 ((R)-N-2-(diphenylacetyl)-N-[(n-hydroxy-phenyl)methyl]-argininamide). The dose-response curves obtained with neuropeptide Y, peptide YY and with C-terminal fragments such as neuropeptide Y-(2-26), neuropeptide Y-(13-36) and peptide YY-(3-36) have similar slopes and maxima. EC50 values of these compounds vary between 30 +/- 10 and 89 +/- 47 nM. The neuropeptide Y Y-1 receptor-selective agonist [Leu(31),Pro(34)]neuropeptide Y and human pancreatic polypeptide are inactive up to 1 mu M. This pharmacological profile suggests that the contraction of the dog saphenous vein induced by neuropeptide Y and its homologues or fragments is mediated by a neuropeptide Y Y-2 receptor type. Moreover, this neuropeptide Y Y-2 receptor appears to be localized in the venous smooth muscle. where it exerts a direct myotropic effect that may be useful for the pharmacological characterization of new compounds acting as agonists or antagonists of the neuropeptide Y Y-2 receptor.