Extracellular Purines in Endothelial Cell Barrier Regulation - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 37

Chapter 3
Extracellular Purines in Endothelial Cell
Barrier Regulation

Nagavedi S. Umapathy, Evgeny A. Zemskov, Agnieszka Jezierska, Irina A.
Kolosova, Rudolf Lucas, John D. Catravas, and Alexander D. Verin

Abstract The vascular endothelium is a semi-selective diffusion barrier that
regulates a variety of functions including controlling of the passage of macro-
molecules 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 reg-
ulators 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 inter-
acting with cell surface P1 and P2Y purinoceptors belonging to the superfamily of
G-protein-coupled receptors (GPCR). Selective activation of endothelial purinore-
ceptors 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 expres-
sion in the endothelium, their interaction with G-proteins and activation of various
signal transduction pathways, which lead to an endothelial barrier enhancement and
protection.

Keywords Purinoceptor · Vascular endothelium · G-Protein · Permeability · ATP ·

Barrier enhancement · VE-cadherin · MLC-phosphatase · GPCR · P2Y · Purines ·

Adenosine · Protein kinase A · LPS

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Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA
e-mail: [e-mail]
Nagavedi S. Umapathy and Evgeny A. Zemskov are equally contributed.
Conflict of Interest : The authors declare no conflicts of interest.

A.D. Verin (