Molecular mechanisms of coronary flow regulation by adenosine
Clinical & Experimental Cardiology

Clinical & Experimental Cardiology
Open Access

ISSN: 2155-9880

Molecular mechanisms of coronary flow regulation by adenosine

5th International Conference on Clinical & Experimental Cardiology

April 27-29, 2015 Philadelphia, USA

S Jamal Mustafa

Scientific Tracks Abstracts: J Clin Exp Cardiolog

Abstract :

Adenosine acts through its receptors (A1, A2A, A2B, and A3) via G-proteins and causes an increase in coronary flow (CF) mostly through A2A AR. However, the role of other ARs in the modulation of CF is not well understood. Using KOs, we investigated the role for each AR in the regulation of CF. Using the isolated heart from A3 KO mice; we reported an increase in A2A-mediated CF. Similarly, we found an increase in CF in A1 KO mice with A2A agonist (CGS-21680). Also, in A2A KO mice, response to CGS was abolished. On the other hand, A2A KO mice showed a decrease in CF to NECA (non-selective agonist). BAY60-6583 (A2B selective agonist) was without an effect on CF in A2B KO mice; however, it increased CF significantly in A2A KO. CGS also caused a significant increase in CF in A2B KO mice. Also, exogenous adenosine-induced increase in CF in WT, A2A KO, and A2B KO mice were significantly reduced with catalase. BAY-induced increase in CF in WT was significantly inhibited with glibenclamide. Overall, our data support stimulatory roles for A2A and A2B and inhibitory roles for A1 and A3 in the regulation of CF. These observations provide new evidence for the presence of all four ARs in CF regulation. We propose, that activation of A2A/B may release H2O2 which then activates KATP channels, leading to vasodilation. These studies may lead to better understanding of the role of ARs in coronary disease and may lead to better therapeutic approaches.

Biography :

S. Jamal Mustafa is an Assistant VP for Research at HSC at West Virginia University (WVU). He received Dean?s Award for Excellence in Research from SOM and became a Robert C. Byrd Professor in 2010 received Chancellor?s Award for Outstanding Achievement in Research and Scholarly Activities from HSC, in 2013. He has published over 190 manuscripts. His past work has led to the approval of an A2A selective AR agonist (Lexican®) for myocardial perfusion imaging. Currently, he is using AR and β adrenergic receptor KOs to better understand the relationship between these receptors in coronary flow regulation.