Contractile effects of neuropeptide Y in human subcutaneous resistance arteries are mediated by Y1 receptors.
The aim of our study was to determine the neuropeptide 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 microM, 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.
Nilsson
T
T
Department of Internal Medicine, Lund University Hospital, Sweden.
Erlinge
D
D
Cantera
L
L
Edvinsson
L
L
D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001158:Arteries / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology; D014661:Vasoconstriction
C092926:BIBP 3226; D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D001120:Arginine