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Potent P2Y6 receptor mediated contractions in human cerebral arteries

Malmsjö, Malin LU ; Hou, Mingyan; Pendergast, William; Erlinge, David LU and Edvinsson, Lars LU (2003) In BMC Pharmacology 3.
Abstract
BACKGROUND: Extracellular nucleotides play an important role in the regulation of vascular tone and may be involved in cerebral vasospasm after subarachnoidal haemorrhage. This study was designed to characterise the contractile P2 receptors in endothelium-denuded human cerebral and omental arteries. The isometric tension of isolated vessel segments was recorded in vitro. P2 receptor mRNA expression was examined by RT-PCR. RESULTS: In human cerebral arteries, the selective P2Y6 receptor agonist, UDPbetaS was the most potent of all the agonists tested (pEC50 = 6.8 PlusMinus; 0.7). The agonist potency; UDPbetaS > alphabeta-MeATP > UTPgammaS > ATPgammaS > ADPbetaS = 0, indicated the presence of contractile P2X1 P2Y2, P2Y4 and P2Y6,... (More)
BACKGROUND: Extracellular nucleotides play an important role in the regulation of vascular tone and may be involved in cerebral vasospasm after subarachnoidal haemorrhage. This study was designed to characterise the contractile P2 receptors in endothelium-denuded human cerebral and omental arteries. The isometric tension of isolated vessel segments was recorded in vitro. P2 receptor mRNA expression was examined by RT-PCR. RESULTS: In human cerebral arteries, the selective P2Y6 receptor agonist, UDPbetaS was the most potent of all the agonists tested (pEC50 = 6.8 PlusMinus; 0.7). The agonist potency; UDPbetaS > alphabeta-MeATP > UTPgammaS > ATPgammaS > ADPbetaS = 0, indicated the presence of contractile P2X1 P2Y2, P2Y4 and P2Y6, but not P2Y1 receptors, in human cerebral arteries. In human omental arteries, UDPbetaS was inactive. The agonist potency; alphabeta-MeATP > ATPgammaS = UTPgammaS > ADPbetaS = UDPbetaS = 0, indicated the presence of contractile P2X1, and P2Y2 receptors, but not P2Y1 or P2Y6 receptors, in human omental arteries. RT-PCR analysis of endothelium-denuded human cerebral and omental arteries demonstrated P2X1, P2Y1, P2Y2 and P2Y6 receptor mRNA expression. There were no bands for the P2Y4 receptor mRNA in the omental arteries, while barely detectable in the cerebral arteries. CONCLUSIONS: P2Y6 receptors play a prominent role in mediating contraction of human cerebral arteries. Conversely, no such effect can be observed in human omental arteries and previous results confirm the absence of P2Y6 receptors in human coronary arteries. The P2Y6 receptor might be a suitable target for the treatment of cerebral vasospasm. (Less)
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organization
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Contribution to journal
publication status
published
subject
in
BMC Pharmacology
volume
3
publisher
BioMed Central
external identifiers
  • pmid:12737633
  • scopus:1642346773
ISSN
2050-6511
DOI
language
English
LU publication?
yes
id
dc0ae8d1-787f-4e60-92c3-b41c1ba55438 (old id 1126177)
date added to LUP
2008-06-11 13:10:55
date last changed
2018-05-29 11:18:33
@article{dc0ae8d1-787f-4e60-92c3-b41c1ba55438,
  abstract     = {BACKGROUND: Extracellular nucleotides play an important role in the regulation of vascular tone and may be involved in cerebral vasospasm after subarachnoidal haemorrhage. This study was designed to characterise the contractile P2 receptors in endothelium-denuded human cerebral and omental arteries. The isometric tension of isolated vessel segments was recorded in vitro. P2 receptor mRNA expression was examined by RT-PCR. RESULTS: In human cerebral arteries, the selective P2Y6 receptor agonist, UDPbetaS was the most potent of all the agonists tested (pEC50 = 6.8 PlusMinus; 0.7). The agonist potency; UDPbetaS > alphabeta-MeATP > UTPgammaS > ATPgammaS > ADPbetaS = 0, indicated the presence of contractile P2X1 P2Y2, P2Y4 and P2Y6, but not P2Y1 receptors, in human cerebral arteries. In human omental arteries, UDPbetaS was inactive. The agonist potency; alphabeta-MeATP > ATPgammaS = UTPgammaS > ADPbetaS = UDPbetaS = 0, indicated the presence of contractile P2X1, and P2Y2 receptors, but not P2Y1 or P2Y6 receptors, in human omental arteries. RT-PCR analysis of endothelium-denuded human cerebral and omental arteries demonstrated P2X1, P2Y1, P2Y2 and P2Y6 receptor mRNA expression. There were no bands for the P2Y4 receptor mRNA in the omental arteries, while barely detectable in the cerebral arteries. CONCLUSIONS: P2Y6 receptors play a prominent role in mediating contraction of human cerebral arteries. Conversely, no such effect can be observed in human omental arteries and previous results confirm the absence of P2Y6 receptors in human coronary arteries. The P2Y6 receptor might be a suitable target for the treatment of cerebral vasospasm.},
  articleno    = {4},
  author       = {Malmsjö, Malin and Hou, Mingyan and Pendergast, William and Erlinge, David and Edvinsson, Lars},
  issn         = {2050-6511},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Pharmacology},
  title        = {Potent P2Y6 receptor mediated contractions in human cerebral arteries},
  url          = {http://dx.doi.org/},
  volume       = {3},
  year         = {2003},
}