Effects of the neuropeptide Y (NPY)-receptor antagonist BIBP3226 on vascular NPY-receptors with different ligand requirements
(1996) In Pharmacology and Toxicology 79(5). p.266-269- 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 < or = 1 microM did not affect the basal tension. Pretreatment with increasing concentrations of BIBP3226 (10 nM-1 microM) 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... (More)
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 < or = 1 microM did not affect the basal tension. Pretreatment with increasing concentrations of BIBP3226 (10 nM-1 microM) 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 (< or = 0.3 microM) evoked a concentration-dependent contraction. Pretreatment with BIBP3226 (0.1 microM) 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.
(Less)
- author
- Grundemar, L LU and Ekelund, M LU
- publishing date
- 1996-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Abdominal Muscles/drug effects, Animals, Arginine/analogs & derivatives, Blood Vessels/drug effects, Guinea Pigs, Humans, In Vitro Techniques, Ligands, Muscle Contraction/drug effects, Muscle, Smooth, Vascular/drug effects, Neuropeptide Y/metabolism, Receptors, Neuropeptide Y/antagonists & inhibitors, Vena Cava, Inferior/drug effects
- in
- Pharmacology and Toxicology
- volume
- 79
- issue
- 5
- pages
- 266 - 269
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:8936561
- scopus:0029853924
- ISSN
- 0901-9928
- DOI
- 10.1111/j.1600-0773.1996.tb00271.x
- language
- English
- LU publication?
- no
- id
- f84def60-ad1c-4b68-b9c7-26c5a2fe0183
- date added to LUP
- 2019-09-03 13:59:42
- date last changed
- 2024-01-01 18:37:51
@article{f84def60-ad1c-4b68-b9c7-26c5a2fe0183,
abstract = {{<p>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 < or = 1 microM did not affect the basal tension. Pretreatment with increasing concentrations of BIBP3226 (10 nM-1 microM) 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 (< or = 0.3 microM) evoked a concentration-dependent contraction. Pretreatment with BIBP3226 (0.1 microM) 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.</p>}},
author = {{Grundemar, L and Ekelund, M}},
issn = {{0901-9928}},
keywords = {{Abdominal Muscles/drug effects; Animals; Arginine/analogs & derivatives; Blood Vessels/drug effects; Guinea Pigs; Humans; In Vitro Techniques; Ligands; Muscle Contraction/drug effects; Muscle, Smooth, Vascular/drug effects; Neuropeptide Y/metabolism; Receptors, Neuropeptide Y/antagonists & inhibitors; Vena Cava, Inferior/drug effects}},
language = {{eng}},
number = {{5}},
pages = {{266--269}},
publisher = {{Wiley-Blackwell}},
series = {{Pharmacology and Toxicology}},
title = {{Effects of the neuropeptide Y (NPY)-receptor antagonist BIBP3226 on vascular NPY-receptors with different ligand requirements}},
url = {{http://dx.doi.org/10.1111/j.1600-0773.1996.tb00271.x}},
doi = {{10.1111/j.1600-0773.1996.tb00271.x}},
volume = {{79}},
year = {{1996}},
}