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 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 x 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)).
Horiuchi
T
T
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Dietrich
H H
HH
Tsugane
S
S
Dacey
R G
RG
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058469:Receptors, Purinergic P2X; D058473:Receptors, Purinergic P2Y2; D013498:Suramin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014530:Uridine Diphosphate / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D000970:Antineoplastic Agents; D020030:Nitric Oxide Donors; C546387:P2ry2 protein, rat; D010975:Platelet Aggregation Inhibitors; D011956:Receptors, Cell Surface; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058473:Receptors, Purinergic P2Y2; D013873:Thionucleotides; C104749:purinoceptor P2Y4; C074644:uridine triphosphate receptors; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D009599:Nitroprusside; D014530:Uridine Diphosphate; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D014544:Uridine Triphosphate; C008501:2-methylthio-ATP