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Contractile effects of neuropeptide Y in human subcutaneous resistance arteries are mediated by Y1 receptors

Nilsson, Torun; Erlinge, David LU ; Cantera, Leonor and Edvinsson, Lars LU (1996) In Journal of Cardiovascular Pharmacology 28(6). p.764-768
Abstract
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Resistance arteries, Neuropeptide Y, Human, BIBP3226, Reverse transcriptase, Polymerase chain reaction
in
Journal of Cardiovascular Pharmacology
volume
28
issue
6
pages
764 - 768
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:8961073
  • scopus:0029850602
ISSN
1533-4023
language
English
LU publication?
yes
id
4066ea92-18f8-4cbd-8a48-0706fecfd862 (old id 1110298)
date added to LUP
2008-07-28 09:36:57
date last changed
2017-07-02 03:29:04
@article{4066ea92-18f8-4cbd-8a48-0706fecfd862,
  abstract     = {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.},
  author       = {Nilsson, Torun and Erlinge, David and Cantera, Leonor and Edvinsson, Lars},
  issn         = {1533-4023},
  keyword      = {Resistance arteries,Neuropeptide Y,Human,BIBP3226,Reverse transcriptase,Polymerase chain reaction},
  language     = {eng},
  number       = {6},
  pages        = {764--768},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Cardiovascular Pharmacology},
  title        = {Contractile effects of neuropeptide Y in human subcutaneous resistance arteries are mediated by Y1 receptors},
  volume       = {28},
  year         = {1996},
}