Opposing effects of ATP and adenosine on barrier function of rat coronary microvasculature

Abstract ATP can differentially affect the micro- and macrovascular endothelial barrier. It has been shown that it can both increase and/or decrease macromolecule permeability of microvascular endothelial cells and microvessels, in vivo . We hypothesised that the barrier stabilising effect is mediat...

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Published in:	Journal of molecular and cellular cardiology Vol. 52; no. 5; pp. 962 - 970
Main Authors:	Gündüz, Dursun, Aslam, Muhammad, Krieger, Uwe, Becker, Lutz, Grebe, Mathias, Arshad, Muhammad, Sedding, Daniel G, Härtel, Frauke V, Abdallah, Yaser, Piper, Hans Michael, Voss, Reinhard K, Noll, Thomas
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-05-2012
Subjects:	Actin Cytoskeleton - drug effects Actin Cytoskeleton - metabolism Adenosine - pharmacology Adenosine 5′-triphosphate Adenosine Diphosphate - pharmacology Adenosine Monophosphate - pharmacology Adenosine receptors Adenosine Triphosphate - pharmacology Adenosine-5'-(N-ethylcarboxamide) - pharmacology Animals Cadherin Cadherins - metabolism Cardiovascular Cells, Cultured Coronary Vessels - cytology Coronary Vessels - drug effects Coronary Vessels - metabolism Coronary Vessels - physiology Edema, Cardiac - pathology Endothelial Cells - drug effects Endothelial Cells - physiology Intravital microscopy Male Myocardium Paracellular permeability Permeability - drug effects Protein Transport - drug effects Purinergic P1 Receptor Agonists - pharmacology Purinergic P1 Receptor Antagonists - pharmacology Purinergic P2 Receptor Antagonists - pharmacology Rats Rats, Wistar Receptors, Purinergic P1 - metabolism Theophylline - analogs & derivatives Theophylline - pharmacology Venules - cytology Venules - drug effects Venules - metabolism Venules - physiology Intravital microscopy Adenosine receptors Cadherin Adenosine 5′-triphosphate Paracellular permeability
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Summary:	Abstract ATP can differentially affect the micro- and macrovascular endothelial barrier. It has been shown that it can both increase and/or decrease macromolecule permeability of microvascular endothelial cells and microvessels, in vivo . We hypothesised that the barrier stabilising effect is mediated by ATP itself via P2 receptors, while barrier-disrupting effect is mediated by its metabolite adenosine via adenosine receptors. The effects of ATP, ADP, AMP and adenosine on barrier function were studied in cultured rat coronary microvascular endothelial monolayers (RCEC) in vitro , as well as in rat mesentery vessels, and in rat hearts in vivo . ATP and ADP showed a biphasic effect on permeability of RCEC monolayers with a reduction followed by a later increase in albumin permeability. The permeability decreasing effect of ATP was enhanced by ecto-nucleotidase inhibitor ARL67156 while permeability increasing effect was enhanced by apyrase, an extracellular ecto-nucleotidase. Moreover, the permeability increasing effect was abrogated by adenosine receptor antagonists, 8-phenyltheophylline (8-PT) and DMPX. Adenosine and adenosine receptor agonists 5′-(N-ethylcarboxamido)-adenosine (NECA), CGS21680, and R-PIA enhanced albumin permeability which was antagonised by 8-PT, A1 , and A2 but not by A3 receptor antagonists. Likewise, immunofluorescence microscopy of VE-cadherin and actin showed that NECA induces a disturbance of intercellular junctions. Pre-incubation of ATP antagonised the effects of NECA on permeability, actin cytoskeleton and intercellular junctions. Similar effects of the applied substances were observed in rat mesentery artery by determining the vascular leakage using intravital microscopy as well as in rat hearts by assessing myocardial water contents in vivo . In conclusion, the study demonstrates that in RCEC, ATP, ADP, and its metabolite adenosine play opposing roles on endothelial barrier function.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-2828 1095-8584
DOI:	10.1016/j.yjmcc.2012.01.003