Contractile Effects of Neuropeptide Y in Human Subcutaneous Resistance Arteries Are Mediated by Y1 Receptors

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Abstract
The aim of our study was to determine the neuropetide Y (NPY) receptor subtype responsible for the NPY-induced contraction of human subcutaneous (s.c.) resistance arteries. To elucidate this, we used (a) in vitro studies of NPY agonists: NPY, peptide YY (PYY), and Pro34NPY induced equally strong and equipotent concentration-dependent contractions of human s.c. resistance arteries, whereas NPY13-36 and NPY18-36 had no contractile effects; (b) in vitro studies using the NPY Y1-receptor antagonist, BIBP3226, which in nanomolar concentrations inhibited the contractile effect of NPY, causing a rightward shift of the concentration-response curve. pEC50 for NPY alone, 8.41 ± 0.21; NPY + BIBP3226, 10 nM, 7.79 ± 0.21; NPY + BIBP3226, 100 nM, 7.18 ± 0.18; NPY + BIBP3226, 1 μM, 6.32 ± 0.05 (n=5-8). Schild-plot analysis indicated competitive antagonism: pA2 = 8.53 ± 0.22 and slope = 0.99 ± 0.14; (c) with reverse transcriptase-polymerase chain reaction (RT-PCR), we detected messenger RNA (mRNA) encoding the human NPY Y1 receptor and a splice variant of the receptor in human s.c. resistance arteries. On the basis of the agonists' potency order, the antagonistic effect of BIBP3226 on the NPY-induced contraction, and the presence of mRNA encoding the NPY Y1 receptor, we conclude that the NPY-induced contraction of human s.c. resistance arteries is mediated by NPY Y1 receptors.