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Professor Malin Malmsjö, MD, PhD. Photo.

Malin Malmsjö

Professor

Professor Malin Malmsjö, MD, PhD. Photo.

P2X receptors counteract the vasodilatory effects of endothelium derived hyperpolarising factor

Author

  • Malin Malmsjö
  • Lars Edvinsson
  • David Erlinge

Summary, in English

Dilatory responses of extracellular nucleotides were examined in the precontracted isolated rat mesenteric artery. Dilatation mediated by endothelium-derived hyperpolarising factor (EDHF) was studied in the presence of Nomega-nitro-L-arginine (L-NOARG) and indomethacin, and was most potently induced by the selective P2Y(1) receptor agonist adenosine 5'-O-thiodiphosphate (ADPbetaS), while 2-methylthioadenosine triphosphate (2-MeSATP) and adenosine triphosphate (ATP) were almost inactive. However, after P2X receptor desensitisation (with alphabeta-methylene-adenosine triphosphate, alphabeta-MeATP), 2-MeSATP and ATP potently stimulated EDHF-mediated dilatation. This can be explained by simultaneous activation of endothelial P2Y receptors that release EDHF, and depolarising P2X receptors on smooth muscle cells. Uridine triphosphate (UTP) also induced potent dilatation, suggesting EDHF release via P2Y(2)/P2Y(4) receptors. Uridine diphosphate (UDP) had only minor dilatory effects, and when pretreated with hexokinase it was almost inactive, suggesting a minor role for P2Y(6) receptors. The nitric oxide (NO) mediated dilatation was studied in the presence of charybdotoxin, apamin and indomethacin. ADPbetaS, 2-MeSATP, ATP and UTP were all potent relaxant agonists suggesting NO release via P2Y(1) and P2Y(2)/P2Y(4) receptors, while UDP was much less potent and efficacious. P2X receptor desensitisation had only minor effect on the NO-mediated dilatations. In conclusion, both EDHF and NO-mediated dilatation can be induced by activation of P2Y(1) and P2Y(2)/P2Y(4) receptors. P2X receptor stimulation of smooth muscle cells selectively counteracts the dilatory effect of EDHF.

Department/s

  • Medicine, Lund
  • Cardiology

Publishing year

2000

Language

English

Pages

173-180

Publication/Series

European Journal of Pharmacology

Volume

390

Issue

1-2

Document type

Journal article

Publisher

Elsevier

Topic

  • Pharmacology and Toxicology

Keywords

  • EDHF (endothelin-derived hyperpolarising factor)
  • Endothelium
  • P2 receptor
  • Purine
  • Pyrimidine
  • Vasodilatation

Status

Published

ISBN/ISSN/Other

  • ISSN: 1879-0712