Inflammatory role of nucleotide P2Y2 receptor: Vascular hyperpermeability

Pharmaceutical Regulatory Affairs: Open Access

ISSN: 2167-7689

Open Access

Inflammatory role of nucleotide P2Y2 receptor: Vascular hyperpermeability

5th International Conference and Exhibition on Pharmaceutical Regulatory Affairs

August 03-05, 2015 Orlando, USA

Jianjie Wang1, Laurie Erb2, Virginia Huxley2, Gary Weisman2 and Richard Garrad1

1Missouri State University, USA 2University of Missouri-Columbia, Columbia

Posters-Accepted Abstracts: Pharmaceut Reg Affairs

Abstract :

Extracellular nucleotides and their cell surface receptors have emerged as key players in inflammation. Hyperpermeability is a hallmark of inflammation and leads to vascular leak resulting in pulmonary edema that often occurs in the intensive care unit (ICU). To date, there is no specific pharmaceutical treatment for edema by a strategy of anti-vascular leakage except expulsion of excess fluid in the form of urine by diuretic drugs. Recently emerging evidence demonstrates nucleotide P2Y2 receptors play important roles in vascular inflammation, including arterial neointimal hyperplasia, increased vascular cell adhesion molecule-1 expression. My in vivo studies revealed that nucleotide P2Y2 receptor activation induced transient 5-fold increase in venular permeability to albumin (Ps) from baseline in wild type (WT) mice, but not in P2Y2 R knockout (P2Y2 R KO) mice. The P2Y2 R signaling-dependent hyperpermeability was mediated by focal adhesion kinase (FAK). Activation P2Y2 R induced phosphorylation of FAK at tyrosine-397 in origin-matched primary cultured murine microvascular endothelial cells. VE-cadherin, a key molecule of the adherens junction present at endothelial cell-cell junctions, increased activity in response to P2Y2 R agonist, UTP, implicating the paracellular pathway contributing to hyperpermeability. Taken together, the findings support nucleotide P2Y2 R play important role in microvascular leak.

Biography :


Google Scholar citation report
Citations: 533

Pharmaceutical Regulatory Affairs: Open Access received 533 citations as per Google Scholar report

Pharmaceutical Regulatory Affairs: Open Access peer review process verified at publons

Indexed In

arrow_upward arrow_upward