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

Anna-Karin Wihlborg; J Slatt; XY Sun; XH Zhao; M Malmsjo; J Bergman; T Hedner; David Erlinge

doi:10.1002/ddr.10205

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

Anna-Karin Wihlborg, J Slatt, XY Sun, XH Zhao, M Malmsjo, J Bergman, T Hedner, David Erlinge

Cardiology

Research output: Chapter in Book/Report/Conference proceeding › Paper in conference proceeding › peer-review

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.

Original language	English
Title of host publication	Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2)
Publisher	John Wiley & Sons Inc.
Pages	82-87
Volume	59
DOIs	https://doi.org/10.1002/ddr.10205
Publication status	Published - 2003
Event	International Symposium on Adenosine and Adenine Nucleotides, 2003 - Gold Coast, Australia Duration: 0001 Jan 2 → … Conference number: 7

Publication series

Name
Number	1
Volume	59
ISSN (Print)	0272-4391
ISSN (Electronic)	1098-2299

Conference

Conference	International Symposium on Adenosine and Adenine Nucleotides, 2003
Country/Territory	Australia
City	Gold Coast
Period	0001/01/02 → …

Subject classification (UKÄ)

Cardiology and Cardiovascular Disease

Free keywords

purines
vasoconstriction
potentiation
P2X receptor
pyrimidines

Access to Document

10.1002/ddr.10205

Cite this

Wihlborg, A.-K., Slatt, J., Sun, XY., Zhao, XH., Malmsjo, M., Bergman, J., Hedner, T., & Erlinge, D. (2003). 2,2 '-nitrophenylisatogen potentiates P2X(1) receptor mediated vascular contraction and blood pressure elevation. In Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2) (Vol. 59, pp. 82-87). John Wiley & Sons Inc.. https://doi.org/10.1002/ddr.10205

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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.",

keywords = "purines, vasoconstriction, potentiation, P2X receptor, pyrimidines",

author = "Anna-Karin Wihlborg and J Slatt and XY Sun and XH Zhao and M Malmsjo and J Bergman and T Hedner and David Erlinge",

year = "2003",

doi = "10.1002/ddr.10205",

language = "English",

volume = "59",

publisher = "John Wiley & Sons Inc.",

number = "1",

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booktitle = "Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2)",

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Wihlborg, A-K, Slatt, J, Sun, XY, Zhao, XH, Malmsjo, M, Bergman, J, Hedner, T & Erlinge, D 2003, 2,2 '-nitrophenylisatogen potentiates P2X(1) receptor mediated vascular contraction and blood pressure elevation. in Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2). vol. 59, John Wiley & Sons Inc., pp. 82-87, International Symposium on Adenosine and Adenine Nucleotides, 2003, Gold Coast, Australia, 0001/01/02. https://doi.org/10.1002/ddr.10205

2,2 '-nitrophenylisatogen potentiates P2X(1) receptor mediated vascular contraction and blood pressure elevation. / Wihlborg, Anna-Karin; Slatt, J; Sun, XY et al.
Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2). Vol. 59 John Wiley & Sons Inc., 2003. p. 82-87.

Research output: Chapter in Book/Report/Conference proceeding › Paper in conference proceeding › peer-review

TY - GEN

T1 - 2,2 '-nitrophenylisatogen potentiates P2X(1) receptor mediated vascular contraction and blood pressure elevation

AU - Wihlborg, Anna-Karin

AU - Slatt, J

AU - Sun, XY

AU - Zhao, XH

AU - Malmsjo, M

AU - Bergman, J

AU - Hedner, T

AU - Erlinge, David

N1 - Conference code: 7

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - purines

KW - vasoconstriction

KW - potentiation

KW - P2X receptor

KW - pyrimidines

U2 - 10.1002/ddr.10205

DO - 10.1002/ddr.10205

M3 - Paper in conference proceeding

VL - 59

SP - 82

EP - 87

BT - Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2)

PB - John Wiley & Sons Inc.

T2 - International Symposium on Adenosine and Adenine Nucleotides, 2003

Y2 - 2 January 0001

ER -

Wihlborg AK, Slatt J, Sun XY, Zhao XH, Malmsjo M, Bergman J et al. 2,2 '-nitrophenylisatogen potentiates P2X(1) receptor mediated vascular contraction and blood pressure elevation. In Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 2). Vol. 59. John Wiley & Sons Inc. 2003. p. 82-87 doi: 10.1002/ddr.10205

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

Abstract

Publication series

Conference

Subject classification (UKÄ)

Free keywords

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