Functional evidence for a novel suramin-insensitive pyrimidine receptor in rat small pulmonary arteries.
Uridine nucleotides are known to cause constriction of pulmonary arterial smooth muscle. However, the P2 receptor subtypes underlying the contractile effects of these nucleotides in the pulmonary circulation have not been determined. We have used myography and the patch-clamp recording technique to compare the effects of UTP and UDP in isolated small pulmonary arteries (diameter 100 to 400 microm) and their constituent smooth muscle cells. In endothelium-denuded arteries, both UTP and UDP (0.01 to 3 mmol/L) induced concentration-dependent increases in tension that were independent of P2X receptor stimulation. The UDP-mediated increase in tension was significantly less sensitive to the nonselective P2 receptor blocker suramin than the UTP-mediated increase in tension. In single isolated arterial myocytes, voltage-clamped at -50 mV (close to the resting membrane potential of these cells), application of both UTP and UDP evoked periodic oscillations of inward current primarily because of a Ca2+-activated Cl- current (ICl,Ca). Oscillations of ICl,Ca evoked by UTP were reversibly inhibited by suramin, although those evoked by UDP were insensitive to the antagonist. In addition to confirming the presence of classical P2Y2 receptors, these results also provide functional evidence for the existence of a novel UDP receptor in pulmonary arterial myocytes, which may contribute to pyrimidine-evoked vasoconstriction. This notion is supported by molecular evidence that demonstrates the presence of P2Y6 receptor transcripts in rat pulmonary arterial smooth muscle.
Hartley
S A
SA
University of Oxford, Department of Pharmacology, Oxford, UK.
Kato
K
K
Salter
K J
KJ
Kozlowski
R Z
RZ
D000818:Animals; D018118:Chloride Channels / Q000187:drug effects; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D013498:Suramin / Q000494:pharmacology*; D014530:Uridine Diphosphate / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D018118:Chloride Channels; D018048:Receptors, Purinergic P2; D014530:Uridine Diphosphate; D013498:Suramin; D014544:Uridine Triphosphate