An investigation of host cell effects on the xenobiotic induction of cytochrome P450 3A

Available from British Library Document Supply Centre-DSC:DXN053303 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

The measurement of needs and the spatial allocation of NHS hospital resources

SIGLEAvailable from British Library Document Supply Centre- DSC:3493.65(CURR-DP--38) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Purinergic 2X receptors mediate endothelial dependent vasodilation to ATP

ATP is an important endogenous mediator in the cardiovascular system. It induces endothelium dependent vasodilation, but the precise receptor pathway activated in this response is currently under debate. We have used traditional bioassay techniques to show that ATP-induced vasodilation in mesenteric vessels is endothelium-dependent. Furthermore, ATP-induced vasodilation was inhibited by both suramin and 2′,3′-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP), consistent with a P2X-, P2X-, or P2X- mediated event and was not potentiated by ivermectin, indicating that these responses were not P2X receptor-mediated. ATP did not induce vasodilation in vessels from P2X mice, confirming an absolute requirement for this receptor. Finally, in pure cell populations of mouse mesenteric artery endothelial cells, we show that P2X mRNA is specifically expressed. However, in line with observations in the brain, the P2X present in endothelial cells does not seem to be recognized by conventional antibodies. Together, these results show that ATP-induced vasodilation is mediated by P2X receptor activation on mesenteric arterial endothelial cells. These observations establish a critical role for P2X receptors in the ATP vasodilator pathway.Peer reviewe