Advanced

2,2 '-nitrophenylisatogen potentiates P2X(1) receptor mediated vascular contraction and blood pressure elevation

Wihlborg, Anna-Karin LU ; Slatt, J; Sun, XY; Zhao, XH; Malmsjo, M; Bergman, J; Hedner, T and Erlinge, David LU (2003) International Symposium on Adenosine and Adenine Nucleotides, 2003 In Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2) 59(1). p.82-87
Abstract
The objective of this research was to examine the effects of chemical compounds with possible P2 receptor modulating effects and to characterize the potentiating effects of 2,2'-nitrophenylisatogen (NPI) on P2X(1) receptors in vitro and in vivo. Chemical compounds were tested in an in vitro pharmacological assay using vascular segments from the rat mesenteric artery stimulated by P2 receptor-specific agonists. Contractions were expressed as a percentage of 60 mM K+-induced contractions. Blood pressure was evaluated in pithed rats. NPI (30 muM) added 15 min before addition of the P2X(1) receptor-specific agonist alphabeta-MeATP increased the maximum vasoconstriction from 23% to 49% (an increase of 113%). Furthermore, NPI prevented the... (More)
The objective of this research was to examine the effects of chemical compounds with possible P2 receptor modulating effects and to characterize the potentiating effects of 2,2'-nitrophenylisatogen (NPI) on P2X(1) receptors in vitro and in vivo. Chemical compounds were tested in an in vitro pharmacological assay using vascular segments from the rat mesenteric artery stimulated by P2 receptor-specific agonists. Contractions were expressed as a percentage of 60 mM K+-induced contractions. Blood pressure was evaluated in pithed rats. NPI (30 muM) added 15 min before addition of the P2X(1) receptor-specific agonist alphabeta-MeATP increased the maximum vasoconstriction from 23% to 49% (an increase of 113%). Furthermore, NPI prevented the desensitization of repeated UP-MeATP contractions. Related compounds were examined, and 2-(3-methoxy-phenyl)-1-oxy-indol-3-one (MPI) had similar effects as NPI, but several others lacked effect. NPI had no effect on ADPbetaS (P2Y(1)) or acetylcholine-mediated vasodilatation, nor on UTP (P2Y(2/4)), UDP (P2Y(6)), or noradrenaline-mediated contractions. In pithed rats, the blood pressure response to 50 nmol/kg-infusion of alphabeta-MeATP was increased from 50+/-6 to 63+/-5 mmHg (P < 0.05), but had no effect on basal blood pressure or on the cardiovascular response to preganglionic nerve stimulation. In conclusion, NPI and MPI potentiates P2X(1) receptor vascular contractions in vitro and (NPI) blood pressure effects in vivo. It is possible that the effect is mediated by an inhibition of P2X(1) receptor desensitization. Drug Dev. Res. (C) Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
purines, vasoconstriction, potentiation, P2X receptor, pyrimidines
in
Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2)
volume
59
issue
1
pages
82 - 87
publisher
John Wiley & Sons
conference name
International Symposium on Adenosine and Adenine Nucleotides, 2003
external identifiers
  • wos:000183384100011
  • scopus:0038651072
ISSN
0272-4391
1098-2299
DOI
language
English
LU publication?
yes
id
1a40041d-f123-45b8-a2a5-f28e57fae94f (old id 309342)
date added to LUP
2007-09-24 08:46:11
date last changed
2018-05-29 09:34:29
@inproceedings{1a40041d-f123-45b8-a2a5-f28e57fae94f,
  abstract     = {The objective of this research was to examine the effects of chemical compounds with possible P2 receptor modulating effects and to characterize the potentiating effects of 2,2'-nitrophenylisatogen (NPI) on P2X(1) receptors in vitro and in vivo. Chemical compounds were tested in an in vitro pharmacological assay using vascular segments from the rat mesenteric artery stimulated by P2 receptor-specific agonists. Contractions were expressed as a percentage of 60 mM K+-induced contractions. Blood pressure was evaluated in pithed rats. NPI (30 muM) added 15 min before addition of the P2X(1) receptor-specific agonist alphabeta-MeATP increased the maximum vasoconstriction from 23% to 49% (an increase of 113%). Furthermore, NPI prevented the desensitization of repeated UP-MeATP contractions. Related compounds were examined, and 2-(3-methoxy-phenyl)-1-oxy-indol-3-one (MPI) had similar effects as NPI, but several others lacked effect. NPI had no effect on ADPbetaS (P2Y(1)) or acetylcholine-mediated vasodilatation, nor on UTP (P2Y(2/4)), UDP (P2Y(6)), or noradrenaline-mediated contractions. In pithed rats, the blood pressure response to 50 nmol/kg-infusion of alphabeta-MeATP was increased from 50+/-6 to 63+/-5 mmHg (P &lt; 0.05), but had no effect on basal blood pressure or on the cardiovascular response to preganglionic nerve stimulation. In conclusion, NPI and MPI potentiates P2X(1) receptor vascular contractions in vitro and (NPI) blood pressure effects in vivo. It is possible that the effect is mediated by an inhibition of P2X(1) receptor desensitization. Drug Dev. Res. (C) Wiley-Liss, Inc.},
  author       = {Wihlborg, Anna-Karin and Slatt, J and Sun, XY and Zhao, XH and Malmsjo, M and Bergman, J and Hedner, T and Erlinge, David},
  booktitle    = {Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2)},
  issn         = {0272-4391},
  keyword      = {purines,vasoconstriction,potentiation,P2X receptor,pyrimidines},
  language     = {eng},
  number       = {1},
  pages        = {82--87},
  publisher    = {John Wiley & Sons},
  title        = {2,2 '-nitrophenylisatogen potentiates P2X(1) receptor mediated vascular contraction and blood pressure elevation},
  url          = {http://dx.doi.org/},
  volume       = {59},
  year         = {2003},
}