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UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors.

Publication ,  Journal Article
Hou, M; Harden, TK; Kuhn, CM; Baldetorp, B; Lazarowski, E; Pendergast, W; Möller, S; Edvinsson, L; Erlinge, D
Published in: Am J Physiol Heart Circ Physiol
February 2002

Mitogenic effects of the extracellular nucleotides ATP and UTP are mediated by P2Y(1), P2Y(2), and P2Y(4) receptors. However, it has not been possible to examine the highly expressed UDP-sensitive P2Y(6) receptor because of the lack of stable, selective agonists. In rat aorta smooth muscle cells (vascular smooth muscle cells; VSMC), UDP and UTP stimulated (3)H-labeled thymidine incorporation with similar pEC(50) values (5.96 and 5.69). Addition of hexokinase did not reduce the mitogenic effect of UDP. In cells transfected with P2Y receptors the stable pyrimidine agonist uridine 5'-O-(2-thiodiphosphate) (UDPbetaS) was specific for P2Y(6) with no effect on P2Y(1), P2Y(2), or P2Y(4) receptors. UDPbetaS stimulated [(3)H]thymidine and [(3)H]leucine incorporation and increased cell number in VSMC. Flow cytometry demonstrated that UDP stimulated cell cycle progression to both the S and G(2) phases. The intracellular signal pathways were dependent on phospholipase C, possibly protein kinase C-delta, and a tyrosine kinase pathway but independent of G(i) proteins, eicosanoids, and protein kinase A. The half-life of P2Y(6) receptor mRNA was <1 h by competitive RT-PCR. The mitogen-activated protein kinase kinase inhibitor PD-098059 significantly suppressed, whereas ATP and interleukin-1beta upregulated, expression of P2Y(6) receptor mRNA. The results demonstrate that UDP stimulates mitogenesis through activation of P2Y(6) receptors and that the receptor is regulated by factors important in the development of vascular disease.

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Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

February 2002

Volume

282

Issue

2

Start / End Page

H784 / H792

Location

United States

Related Subject Headings

  • Uridine Triphosphate
  • Uridine Diphosphate
  • Type C Phospholipases
  • Tritium
  • Thymidine
  • Thionucleotides
  • Receptors, Purinergic P2
  • Rats, Sprague-Dawley
  • Rats
  • Purinergic P2 Receptor Agonists
 

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Hou, M., Harden, T. K., Kuhn, C. M., Baldetorp, B., Lazarowski, E., Pendergast, W., … Erlinge, D. (2002). UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors. Am J Physiol Heart Circ Physiol, 282(2), H784–H792. https://doi.org/10.1152/ajpheart.00997.2000
Hou, Mingyan, T Kendall Harden, Cynthia M. Kuhn, Bo Baldetorp, Eduardo Lazarowski, William Pendergast, Sebastian Möller, Lars Edvinsson, and David Erlinge. “UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors.Am J Physiol Heart Circ Physiol 282, no. 2 (February 2002): H784–92. https://doi.org/10.1152/ajpheart.00997.2000.
Hou M, Harden TK, Kuhn CM, Baldetorp B, Lazarowski E, Pendergast W, et al. UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors. Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H784–92.
Hou, Mingyan, et al. “UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors.Am J Physiol Heart Circ Physiol, vol. 282, no. 2, Feb. 2002, pp. H784–92. Pubmed, doi:10.1152/ajpheart.00997.2000.
Hou M, Harden TK, Kuhn CM, Baldetorp B, Lazarowski E, Pendergast W, Möller S, Edvinsson L, Erlinge D. UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors. Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H784–H792.

Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

February 2002

Volume

282

Issue

2

Start / End Page

H784 / H792

Location

United States

Related Subject Headings

  • Uridine Triphosphate
  • Uridine Diphosphate
  • Type C Phospholipases
  • Tritium
  • Thymidine
  • Thionucleotides
  • Receptors, Purinergic P2
  • Rats, Sprague-Dawley
  • Rats
  • Purinergic P2 Receptor Agonists