Functional Evidence for a Novel Suramin-Insensitive Pyrimidine Receptor in Rat Small Pulmonary Arteries

From the University of Oxford, Department of Pharmacology, Oxford, UK.

Correspondence to Roland Z. Kozlowski, University Department of Pharmacology, Mansfield Rd, Oxford, OX1 3QT, UK. E-mail roland.kozlowski{at}pharm.ox.ac.uk

Abstract—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 µm) 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 (I_Cl,Ca). Oscillations of I_Cl,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.

Key Words: artery, pulmonary • nucleotide, uridine • channel, Cl^-

This article has been cited by other articles:

				I. Bar, P.-J. Guns, J. Metallo, D. Cammarata, F. Wilkin, J.-M. Boeynams, H. Bult, and B. Robaye Knockout Mice Reveal a Role for P2Y6 Receptor in Macrophages, Endothelial Cells, and Vascular Smooth Muscle Cells Mol. Pharmacol., September 1, 2008; 74(3): 777 - 784. [Abstract] [Full Text] [PDF]

				Y. Gui, M. P. Walsh, V. Jankowski, J. Jankowski, and X.-L. Zheng Up4A stimulates endothelium-independent contraction of isolated rat pulmonary artery Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L733 - L738. [Abstract] [Full Text] [PDF]

				N. L. Jernigan, B. R. S. Broughton, B. R. Walker, and T. C. Resta Impaired NO-dependent inhibition of store- and receptor-operated calcium entry in pulmonary vascular smooth muscle after chronic hypoxia Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L517 - L525. [Abstract] [Full Text] [PDF]

				C. Vial and R. J. Evans P2X1 Receptor-Deficient Mice Establish the Native P2X Receptor and a P2Y6-Like Receptor in Arteries Mol. Pharmacol., December 1, 2002; 62(6): 1438 - 1445. [Abstract] [Full Text] [PDF]

				T. Horiuchi, H. H. Dietrich, S. Tsugane, and R. G. Dacey Jr. Analysis of purine- and pyrimidine-induced vascular responses in the isolated rat cerebral arteriole Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H767 - H776. [Abstract] [Full Text] [PDF]

				C J Lewis, S J Ennion, and R J Evans P2 purinoceptor-mediated control of rat cerebral (pial) microvasculature; contribution of P2X and P2Y receptors J. Physiol., September 1, 2000; 527(2): 315 - 324. [Abstract] [Full Text] [PDF]

				J. L. Bouchie, H.-C. Chen, R. Carney, J. C. Bagot, P. A. Wilden, and E. P. Feener P2Y Receptor Regulation of PAI-1 Expression in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 866 - 873. [Abstract] [Full Text] [PDF]