Analysis of purine- and pyrimidine-induced vascular responses in the isolated rat cerebral arteriole

Effects of extraluminal UTP were studied and compared with vascular responses to ATP and its analogs in rat cerebral-penetrating arterioles. UTP, UDP, 2-methylthio-ATP, and α,β-methylene-ATP dilated arterioles at the lowest concentration and constricted them at high concentrations. Low concentrations of ATP dilated the vessels; high concentrations caused a biphasic response, with transient constriction followed by dilation. Endothelial impairment inhibited ATP- and UTP-mediated dilation and potentiated constriction to UTP but not to ATP. ATP- and 2-methylthio-ATP- but not UTP-mediated constrictions were inhibited by desensitization with 10^-6 M α,β-methylene-ATP or 3 × 10^-6 M pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS). PPADS at 10^-4 M abolished the UTP-mediated constriction and induced vasodilation in a dose-dependent manner but did not affect the dilation to ATP. These results suggest that in rat cerebral microvessels 1) ATP and 2-methylthio-ATP induce transient constriction via smooth muscle P_2X1 receptors in the cerebral arteriole, 2) UTP stimulates two different classes of P_2Y receptors, resulting in constriction (smooth muscle P_2Y4) and dilation (possibly endothelial P_2Y2), and 3) ATP and UTP produce dilation by stimulation of a single receptor (P_2Y2).