Potent P2Y6 receptor mediated contractions in human cerebral arteries.
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.
Malmsjö
Malin
M
Division of Experimental Vascular Research, Department of Internal Medicine, Lund University Hospital, Lund, Sweden. malin.malmsjo@med.lu.se
Hou
Mingyan
M
Pendergast
William
W
Erlinge
David
D
Edvinsson
Lars
L
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate