Extracellular purines in endothelial cell barrier regulation

Umapathy N Siddaramappa, Evgeny Alexandrovich Zemskov, Agnieszka Jezierska, Irina A. Kolosova, Rudolf Lucas, John D. Catravas, Alexander Dmitriyevich Verin

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The vascular endothelium is a semi-selective diffusion barrier that regulates a variety of functions including controlling of the passage of macromolecules and fluid between the blood and interstitial fluid. It is well known that loss of this barrier (permeability increase) results in tissue inflammation, the hall mark of inflammatory diseases such as acute lung injury (ALI) and a severe form of it, acute respiratory distress syndrome (ARDS). Apart from ventilation strategies, no standard treatment exists for ALI and ARDS, making the search for novel regulators of endothelial hyperpermeability and dysfunction important. Accumulating data suggest that extracellular purines are promising and physiologically relevant barrier-protective agents. Purines decrease transendothelial permeability by interacting with cell surface P1 and P2Y purinoceptors belonging to the superfamily of G-protein-coupled receptors (GPCR). Selective activation of endothelial purinoreceptors responsible for barrier protection might form a basis for the treatment of various disorders. The therapeutic potential of purinoreceptors is rapidly expanding field in pharmacology and some selective agonists became recently available. In this review, we demonstrate the comprehensive overview of the purinoceptors expression in the endothelium, their interaction with G-proteins and activation of various signal transduction pathways, which lead to an endothelial barrier enhancement and protection.

Original languageEnglish (US)
Title of host publicationExtracellular ATP and Adenosine as Regulators of Endothelial Cell Function
Subtitle of host publicationImplications for Health and Disease
PublisherSpringer Netherlands
Pages39-55
Number of pages17
ISBN (Print)9789048134342
DOIs
StatePublished - Dec 1 2010

Keywords

  • ATP
  • Adenosine
  • Barrier enhancement
  • G-Protein
  • GPCR
  • LPS
  • MLC-phosphatase
  • P2Y
  • Permeability
  • Protein kinase A
  • Purines
  • Purinoceptor
  • VE-cadherin
  • Vascular endothelium

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Siddaramappa, U. N., Zemskov, E. A., Jezierska, A., Kolosova, I. A., Lucas, R., Catravas, J. D., & Verin, A. D. (2010). Extracellular purines in endothelial cell barrier regulation. In Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function: Implications for Health and Disease (pp. 39-55). Springer Netherlands. https://doi.org/10.1007/978-90-481-3435-9_3