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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/114257
- author
- Wihlborg, Anna-Karin
LU
; Malmsjö, Malin
LU
; Eyjolfsson, Atli
LU
; Gustafsson, Ronny
LU
; Jacobson, Kenneth
and Erlinge, David
LU
- organization
- publishing date
- 2003
- 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
- Wiley
- 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
- 2016-04-01 15:45:32
- date last changed
- 2024-01-10 19:09:25
@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}},
keywords = {{endothelium-derived hyperpolarising factor; human; nitric oxide; nucleotide; vasodilatation; P2 receptor; endothelium; coronary circulation}},
language = {{eng}},
number = {{8}},
pages = {{1451--1458}},
publisher = {{Wiley}},
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}},
doi = {{10.1038/sj.bjp.0705186}},
volume = {{138}},
year = {{2003}},
}