Effects of the Neuropeptide Y (NPY)‐Receptor Antagonist BIBP3226 on Vascular NPY‐Receptors with Different Ligand Requirements

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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 ≤1μM did not affect the basal tension. Pretreatment with increasing concentrations of BIBP3226 (10 nM ‐ 1 μM) 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 (≤0.3μM) evoked a concentration‐dependent contraction. Pretreatment with BIBP3226 (0.1 μM) 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.

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