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Am J Physiol Heart Circ Physiol 280: H767-H776, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 2, H767-H776, February 2001

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

Tetsuyoshi Horiuchi, Hans H. Dietrich, Shinichiro Tsugane, and Ralph G. Dacey Jr.

Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri 63110

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 alpha ,beta -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 alpha ,beta -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 P2X1 receptors in the cerebral arteriole, 2) UTP stimulates two different classes of P2Y receptors, resulting in constriction (smooth muscle P2Y4) and dilation (possibly endothelial P2Y2), and 3) ATP and UTP produce dilation by stimulation of a single receptor (P2Y2).

ATP; cerebral circulation; UTP; purine receptors; pyrimidine receptors


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