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ADP Receptor P2Y12 Is Expressed in Vascular Smooth Muscle Cells and Stimulates Contraction in Human Blood Vessels.

Wihlborg, Anna-Karin LU ; Wang, Lingwei LU ; Braun, Oscar Ostberg; Eyjolfsson, Atli LU ; Gustafsson, Ronny LU ; Gudbjartsson, Tomas and Erlinge, David LU (2004) In Arteriosclerosis, Thrombosis and Vascular Biology 24(10). p.1810-1815
Abstract
Objective - ADP plays an important role in platelet aggregation by activating P2Y(12) receptors. We assessed the hypothesis that P2Y(12) receptors are expressed in vascular smooth muscle cells (VSMC). Methods and Results - P2Y(12) receptor mRNA was found to have a high expression among the P2 receptors in human VSMC, significantly higher than the other 2 ADP receptors (P2Y(1) and P2Y(13), real-time polymerase chain reaction). Western blots gave a band of 50 kD, similar to that in platelets. To unmask a P2Y(12) receptor-mediated vasoconstriction by simulating the in vivo situation, vessels were precontracted to a submaximal level. 2-MeSADP stimulated contractions in vessel segments from internal mammary artery (IM), IM branches and small... (More)
Objective - ADP plays an important role in platelet aggregation by activating P2Y(12) receptors. We assessed the hypothesis that P2Y(12) receptors are expressed in vascular smooth muscle cells (VSMC). Methods and Results - P2Y(12) receptor mRNA was found to have a high expression among the P2 receptors in human VSMC, significantly higher than the other 2 ADP receptors (P2Y(1) and P2Y(13), real-time polymerase chain reaction). Western blots gave a band of 50 kD, similar to that in platelets. To unmask a P2Y(12) receptor-mediated vasoconstriction by simulating the in vivo situation, vessels were precontracted to a submaximal level. 2-MeSADP stimulated contractions in vessel segments from internal mammary artery (IM), IM branches and small veins (E-max = 15 +/- 6% of 60 mmol/L K+ contraction, pEC(50) = 5.6 +/- 0.6, E-max = 21 +/- 1%, pEC(50) = 6.8 +/- 0.1, and E-max = 48 +/- 9%, pEC(50) = 6.6 +/- 0.4). The selective P2Y(12) antagonist AR-C67085 blocked 2-MeSADP contractions. The contraction was not reduced in patients using clopidogrel, a drug inhibiting ADP-induced platelet aggregation by blocking the P2Y(12) receptor. This may be explained by the high instability of the active clopidogrel metabolite that never reaches the systemic circulation. Conclusion - ADP acting on P2Y(12) receptors not only is important for platelet activation but also stimulates vasoconstriction. Stable drugs with antagonistic effects on P2Y(12) receptors, affecting both platelets and VSMC, could be of double therapeutic benefit in their prevention of both thrombosis and vasospasm. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
vasoconstriction, platelets, ADP, P2Y receptors
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
24
issue
10
pages
1810 - 1815
publisher
American Heart Association
external identifiers
  • pmid:15308557
  • wos:000224326200013
  • scopus:5344257562
ISSN
1524-4636
DOI
10.1161/01.ATV.0000142376.30582.ed
language
English
LU publication?
yes
id
7b14be01-9a01-4df1-916f-5137fd7bfcfa (old id 126721)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15308557&dopt=Abstract
date added to LUP
2007-07-02 13:29:04
date last changed
2017-11-12 03:19:42
@article{7b14be01-9a01-4df1-916f-5137fd7bfcfa,
  abstract     = {Objective - ADP plays an important role in platelet aggregation by activating P2Y(12) receptors. We assessed the hypothesis that P2Y(12) receptors are expressed in vascular smooth muscle cells (VSMC). Methods and Results - P2Y(12) receptor mRNA was found to have a high expression among the P2 receptors in human VSMC, significantly higher than the other 2 ADP receptors (P2Y(1) and P2Y(13), real-time polymerase chain reaction). Western blots gave a band of 50 kD, similar to that in platelets. To unmask a P2Y(12) receptor-mediated vasoconstriction by simulating the in vivo situation, vessels were precontracted to a submaximal level. 2-MeSADP stimulated contractions in vessel segments from internal mammary artery (IM), IM branches and small veins (E-max = 15 +/- 6% of 60 mmol/L K+ contraction, pEC(50) = 5.6 +/- 0.6, E-max = 21 +/- 1%, pEC(50) = 6.8 +/- 0.1, and E-max = 48 +/- 9%, pEC(50) = 6.6 +/- 0.4). The selective P2Y(12) antagonist AR-C67085 blocked 2-MeSADP contractions. The contraction was not reduced in patients using clopidogrel, a drug inhibiting ADP-induced platelet aggregation by blocking the P2Y(12) receptor. This may be explained by the high instability of the active clopidogrel metabolite that never reaches the systemic circulation. Conclusion - ADP acting on P2Y(12) receptors not only is important for platelet activation but also stimulates vasoconstriction. Stable drugs with antagonistic effects on P2Y(12) receptors, affecting both platelets and VSMC, could be of double therapeutic benefit in their prevention of both thrombosis and vasospasm.},
  author       = {Wihlborg, Anna-Karin and Wang, Lingwei and Braun, Oscar Ostberg and Eyjolfsson, Atli and Gustafsson, Ronny and Gudbjartsson, Tomas and Erlinge, David},
  issn         = {1524-4636},
  keyword      = {vasoconstriction,platelets,ADP,P2Y receptors},
  language     = {eng},
  number       = {10},
  pages        = {1810--1815},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {ADP Receptor P2Y12 Is Expressed in Vascular Smooth Muscle Cells and Stimulates Contraction in Human Blood Vessels.},
  url          = {http://dx.doi.org/10.1161/01.ATV.0000142376.30582.ed},
  volume       = {24},
  year         = {2004},
}