title: Enhanced A2A adenosine receptor-mediated increase in coronary flow in type I diabetic mice.
abstract: Adenosine A2A receptor (A2AAR) activation plays a major role in the regulation of coronary flow (CF). Recent studies from our laboratory and others have suggested that A2AAR expression and/or signaling is altered in disease conditions. However, the coronary response to AR activation, in particular A2AAR, in diabetes is not fully understood. In this study, we use an STZ mouse model of type 1 diabetes (T1D) to look at CF responses to the nonspecific AR agonist NECA and the A2AAR specific agonist CGS 21680 in-vivo and ex-vivo. Using immunofluorescence, we also explored the effect of diabetes on A2AAR expression in coronary arteries. NECA mediated increase in CF was significantly increased in hearts isolated from STZ-induced diabetic mice. In addition, both in in-vivo and ex-vivo responses to A2AAR activation using CGS 21680 were significantly higher in diabetic mice when compared to their controls. Immunohistochemistry showed an upregulation of A2AAR in both coronary smooth muscle and endothelial cells (~160% and ~140%, respectively). Our data suggest that diabetes resulted in an increased A2AAR expression in coronary arteries which resulted in enhanced A2AAR-mediated increase in CF observed in diabetic hearts. This is the first report implying that A2AAR has a role in the regulation of CF in diabetes, supporting recent studies suggesting that the use of adenosine and its A2A selective agonist (regadenoson, Lexiscan®) may not be appropriate for the detection of coronary artery diseases in T1D and the estimation of coronary reserve.
authors.affiliation: Department of Physiology and Pharmacology, Center for Cardiovascular and Respiratory Sciences and Clinical Translational Science Institute, West Virginia University, Morgantown, WV, United States.
authors.forename: Hicham
authors.initials: H
authors.lastname: Labazi
authors.affiliation: Department of Physiology and Pharmacology, Center for Cardiovascular and Respiratory Sciences and Clinical Translational Science Institute, West Virginia University, Morgantown, WV, United States.
authors.forename: Bunyen
authors.initials: B
authors.lastname: Teng
authors.affiliation: Department of Physiology and Pharmacology, Center for Cardiovascular and Respiratory Sciences and Clinical Translational Science Institute, West Virginia University, Morgantown, WV, United States.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Pharmacology, Center for Cardiovascular and Respiratory Sciences and Clinical Translational Science Institute, West Virginia University, Morgantown, WV, United States. Electronic address: sjmustafa@hsc.wvu.edu.
authors.forename: S Jamal
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D010627:Phenethylamines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000235:genetics* / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D014665:Vasodilator Agents; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine
keywords: A(2A) adenosine receptor; CGS 21680; Diabetes; NECA; coronary flow