Potent P2Y(6 )receptor mediated contractions in human cerebral arteries

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 P2Y(6 )receptor agonist, UDPβS was the most potent of all the agonists tested (pEC(50 )= 6.8 ± 0.7). The agonist potency; UDPβS > αβ-MeATP > UTPγS > ATPγS > ADPβS = 0, indicated the presence of contractile P2X(1 )P2Y(2), P2Y(4 )and P2Y(6), but not P2Y(1 )receptors, in human cerebral arteries. In human omental arteries, UDPβS was inactive. The agonist potency; αβ-MeATP > ATPγS = UTPγS > ADPβS = UDPβS = 0, indicated the presence of contractile P2X(1), and P2Y(2 )receptors, but not P2Y(1 )or P2Y(6 )receptors, in human omental arteries. RT-PCR analysis of endothelium-denuded human cerebral and omental arteries demonstrated P2X(1), P2Y(1), P2Y(2 )and P2Y(6 )receptor mRNA expression. There were no bands for the P2Y(4 )receptor mRNA in the omental arteries, while barely detectable in the cerebral arteries. CONCLUSIONS: P2Y(6 )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 P2Y(6 )receptors in human coronary arteries. The P2Y(6 )receptor might be a suitable target for the treatment of cerebral vasospasm