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Scand Cardiovasc J. 2018 Nov 27:1-7. doi: 10.1080/14017431.2018.1552793. [Epub ahead of print]

Role of Pannexin and adenosine triphosphate (ATP) following myocardial ischemia/reperfusion.

Author information

1
a Department of Clinical Experimental Research , Glostrup Research Institute, Copenhagen University Hospital , Rigshospitalet- Glostrup , Denmark.
2
b Department of Drug Design and Pharmacology, Faculty of Health Sciences , University of Copenhagen , Denmark.
3
c Current address: Experimental Pharmacology and Toxicology , Section of Experimental Animal Models , Department of Veterinary and Animal Sciences , University of Copenhagen , Denmark.
4
d Department of Pediatrics , Glostrup Research Institute, Copenhagen University Hospital , Glostrup , Denmark.
5
e Current address: Center for Genomic Medicine, Copenhagen University Hospital , Denmark.

Abstract

OBJECTIVES:

The purinergic system has not been investigated in detail following ischemia/reperfusion (I/R) injury in the heart. In the present study we focus on both release and response to extracellular adenosine triphosphate (ATP). Pannexin (Panx) channels have been shown to be involved in ATP release from myocytes and can activate P2X1 and P2Y2 receptors on the coronary artery.

DESIGN:

We applied a well characterized I/R model in rats, with 24 hours of reperfusion. Panx expression in the myocardial tissue was measured with quantitative polymerase chain reaction (qPCR) and flow cytometry. ATP release was detected in situ using luminescence and the vascular response to nucleotides determined in a wire myograph.

RESULTS:

Here we show that Panx expression is increased after experimental myocardial I/R, leading to an increase in extracellular ATP release, which could be inhibited by probenecid. Functional studies revealed that the P2Y2 receptor dependent contraction is reduced in the coronary artery after I/R, which might be a response to the increased ATP levels.

CONCLUSION:

We therefore, conclude that the regulation of the arterial purinergic system minimizes coronary contractions following ischemia.

KEYWORDS:

Ischemia/reperfusion; coronary artery; myograph; pannexin; purinergic receptors

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