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Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factor.

Wihlborg, Anna-Karin LU ; Malmsjö, Malin LU ; Eyjolfsson, Atli LU ; Gustafsson, Ronny LU ; Jacobson, Kenneth and Erlinge, David LU (2003) In British Journal of Pharmacology 138(8). p.1451-1458
Abstract
1. The present study was aimed at examining P2 receptor-mediated vasodilatation in human vessels. The isometric tension was recorded in isolated segments of the human left internal mammary artery branches precontracted with 1 muM noradrenaline.

2. Endothelial denudation abolished the dilator responses.

3. The selective P2Y1 agonist, 2-MeSADP, induced a potent vasodilatation (pEC50=6.9plusminus0.1). The P2Y1 antagonist of 10 muM, MRS 2216, shifted the 2-MeSADP concentration-response curve 1.1 log units to the right. The combined P2Y1 and P2X agonist, 2-MeSATP, stimulated a dilatation with a potency similar to that of 2-MeSADP. Furthermore, MRS 2216 had a similar antagonistic effect on both 2-MeSATP and 2-MeSADP... (More)
1. The present study was aimed at examining P2 receptor-mediated vasodilatation in human vessels. The isometric tension was recorded in isolated segments of the human left internal mammary artery branches precontracted with 1 muM noradrenaline.

2. Endothelial denudation abolished the dilator responses.

3. The selective P2Y1 agonist, 2-MeSADP, induced a potent vasodilatation (pEC50=6.9plusminus0.1). The P2Y1 antagonist of 10 muM, MRS 2216, shifted the 2-MeSADP concentration-response curve 1.1 log units to the right. The combined P2Y1 and P2X agonist, 2-MeSATP, stimulated a dilatation with a potency similar to that of 2-MeSADP. Furthermore, MRS 2216 had a similar antagonistic effect on both 2-MeSATP and 2-MeSADP indicating that P2X receptors do not mediate vasodilatation.

4. Both the P2Y2/4 agonist, UTPitalic gammaS and the P2Y6 agonist, UDPbetaS, stimulated potent dilatations (pEC50=7.8plusminus0.4 for UTPitalic gammaS and 8.4plusminus0.2 for UDPbetaS).

5. The 2-MeSADP-induced nitric oxide (NO)-mediated dilatation was studied in the presence of 10 muM indomethacin, 50 nM charybdotoxin and 1 muM apamin. The involvement of the endothelium-derived hyperpolarising factor (EDHF) was investigated in the presence of 0.1 mML-NOARG and indomethacin. The involvement of prostaglandins was investigated in the presence of L-NOARG, charybdotoxin and apamin. Both NO, EDHF and prostaglandins mediated 2-MeSADP dilatation with similar efficacy (Emax=25plusminus5% for NO, 25plusminus6% for EDHF and 27plusminus5% for prostaglandins).

6. In conclusion, extracellular nucleotides induce endothelium-derived vasodilatation in human vessels by stimulating P2Y1, P2Y2/4 and P2Y6 receptors, while P2X receptors are not involved. Endothelial P2Y receptors mediate dilatation by release of EDHF, NO and prostaglandins (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
endothelium-derived hyperpolarising factor, human, nitric oxide, nucleotide, vasodilatation, P2 receptor, endothelium, coronary circulation
in
British Journal of Pharmacology
volume
138
issue
8
pages
1451 - 1458
publisher
The British Pharmacological Society
external identifiers
  • wos:000182969900009
  • pmid:12721100
  • scopus:0038630484
ISSN
1476-5381
DOI
10.1038/sj.bjp.0705186
language
English
LU publication?
yes
id
27ca81b6-d4b1-43bb-9efa-8ff6365f0312 (old id 114257)
date added to LUP
2007-06-26 13:17:15
date last changed
2018-09-09 04:15:31
@article{27ca81b6-d4b1-43bb-9efa-8ff6365f0312,
  abstract     = {1. The present study was aimed at examining P2 receptor-mediated vasodilatation in human vessels. The isometric tension was recorded in isolated segments of the human left internal mammary artery branches precontracted with 1 muM noradrenaline.<br/><br>
 2. Endothelial denudation abolished the dilator responses.<br/><br>
 3. The selective P2Y1 agonist, 2-MeSADP, induced a potent vasodilatation (pEC50=6.9plusminus0.1). The P2Y1 antagonist of 10 muM, MRS 2216, shifted the 2-MeSADP concentration-response curve 1.1 log units to the right. The combined P2Y1 and P2X agonist, 2-MeSATP, stimulated a dilatation with a potency similar to that of 2-MeSADP. Furthermore, MRS 2216 had a similar antagonistic effect on both 2-MeSATP and 2-MeSADP indicating that P2X receptors do not mediate vasodilatation.<br/><br>
 4. Both the P2Y2/4 agonist, UTPitalic gammaS and the P2Y6 agonist, UDPbetaS, stimulated potent dilatations (pEC50=7.8plusminus0.4 for UTPitalic gammaS and 8.4plusminus0.2 for UDPbetaS).<br/><br>
 5. The 2-MeSADP-induced nitric oxide (NO)-mediated dilatation was studied in the presence of 10 muM indomethacin, 50 nM charybdotoxin and 1 muM apamin. The involvement of the endothelium-derived hyperpolarising factor (EDHF) was investigated in the presence of 0.1 mML-NOARG and indomethacin. The involvement of prostaglandins was investigated in the presence of L-NOARG, charybdotoxin and apamin. Both NO, EDHF and prostaglandins mediated 2-MeSADP dilatation with similar efficacy (Emax=25plusminus5% for NO, 25plusminus6% for EDHF and 27plusminus5% for prostaglandins).<br/><br>
 6. In conclusion, extracellular nucleotides induce endothelium-derived vasodilatation in human vessels by stimulating P2Y1, P2Y2/4 and P2Y6 receptors, while P2X receptors are not involved. Endothelial P2Y receptors mediate dilatation by release of EDHF, NO and prostaglandins},
  author       = {Wihlborg, Anna-Karin and Malmsjö, Malin and Eyjolfsson, Atli and Gustafsson, Ronny and Jacobson, Kenneth and Erlinge, David},
  issn         = {1476-5381},
  keyword      = {endothelium-derived hyperpolarising factor,human,nitric oxide,nucleotide,vasodilatation,P2 receptor,endothelium,coronary circulation},
  language     = {eng},
  number       = {8},
  pages        = {1451--1458},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factor.},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0705186},
  volume       = {138},
  year         = {2003},
}