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

Research output: Chapter in Book/Report/Conference proceedingPaper in conference proceeding

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 < 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.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems

Keywords

  • purines, vasoconstriction, potentiation, P2X receptor, pyrimidines
Original languageEnglish
Title of host publicationDrug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2)
PublisherJohn Wiley and Sons Inc.
Pages82-87
Volume59
Publication statusPublished - 2003
Publication categoryResearch
Peer-reviewedYes
EventInternational Symposium on Adenosine and Adenine Nucleotides, 2003 - Gold Coast, Australia
Duration: 0001 Jan 2 → …
Conference number: 7

Publication series

Name
Number1
Volume59
ISSN (Print)0272-4391
ISSN (Electronic)1098-2299

Conference

ConferenceInternational Symposium on Adenosine and Adenine Nucleotides, 2003
CountryAustralia
CityGold Coast
Period0001/01/02 → …