Purinergic receptors in human placenta

Evidence for functionally active P2X4, P2X7, P2Y2, and P2Y6

Victoria Roberts, S. L. Greenwood, A. C. Elliott, C. P. Sibley, L. H. Waters

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Appropriate regulation of ion transport by the human placental syncytiotrophoblast is important for fetal growth throughout pregnancy. In nonplacental tissues, ion transport can be modulated by extracellular nucleotides that raise intracellular calcium ([Ca2+]i) via activation of purinergic receptors. We tested the hypothesis that purinergic receptors are expressed by human placental cytotrophoblast cells and that their activation by extracellular nucleotides modulates ion (K+) efflux and [Ca2+]i. P2X/P2Y receptor agonists 5-bromouridine 5′-triphosphate (5-BrUTP), ADP, ATP, 2′,3′-O-(4-benzoyl- benzoyl)adenosine 5′-triphosphate (BzATP), and UTP stimulated 86Rb (K+ tracer) efflux from cultured cytotrophoblast cells at early (mononuclear) or later (multinucleate syncytiotrophoblast-like) stages of differentiation, with ATP and UTP particularly potent. 2-Methylthioadenosine 5′-triphosphate (2-MeS-ATP), and UDP elevated 86Rb efflux only from multinucleated cells. All agonists caused a significant peak and plateau increase in [Ca2+]i, although the magnitude of responses was variable. The effect of BzATP, UTP, and UDP in multinucleated cells was unaffected, and that of ATP partially inhibited, by removal of extracellular Ca2+, implicating P2Y receptor activation. mRNA encoding P2X1, P2X2, P2X4, and P2X 7 and P2Y1, P2Y2, P2Y4, P2Y 6, and P2Y11 were identified in mono- and multinucleated cells, whereas P2X3 and P2X5 mRNA were absent from all samples. Western blot analysis revealed P2X4, P2X7, P2Y2, and P2Y6 protein in cytotrophoblast cells, but P2Y4 was not detected. On the basis of published agonist selectivity, the data indicate the presence of functionally active P2X4, P2X 7, P2Y2, and P2Y6 receptors in cytotrophoblast cells. We propose that activation of these receptors, and subsequent elevation of [Ca2+]i, modulates syncytiotrophoblast homeostasis and/or maternofetal ion exchange in response to extracellular nucleotides.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume290
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

Purinergic Receptors
Trophoblasts
Placenta
Adenosine Triphosphate
Uridine Triphosphate
Uridine Diphosphate
Nucleotides
Ion Transport
Purinergic P2Y2 Receptors
Messenger RNA
Ion Exchange
Fetal Development
Adenosine Diphosphate
Cultured Cells
Homeostasis
Western Blotting
Ions
Calcium
Pregnancy

Keywords

  • Calcium
  • Cytotrophoblast
  • Potassium

ASJC Scopus subject areas

  • Physiology

Cite this

Purinergic receptors in human placenta : Evidence for functionally active P2X4, P2X7, P2Y2, and P2Y6. / Roberts, Victoria; Greenwood, S. L.; Elliott, A. C.; Sibley, C. P.; Waters, L. H.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 290, No. 5, 05.2006.

Research output: Contribution to journalArticle

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