My laboratory’s research is focused on the role of G protein coupled receptor (GPCR) regulation of cardiac function and response to stress, such as myocardial ischemia-reperfusion. Our primary focus is the adenosine receptor system, which is composed of four receptor subtypes. All four subtypes are expressed to varying degrees in cardiac myocytes, fibroblasts, and endothelial cells in mammalian myocardium. We are currently examining interactions among these receptor subtypes in the reduction of myocardial ischemia-reperfusion injury, as well as interactions among adenosine receptors and other GPCR, such as beta-adrenergic receptors and opioid receptors. These interactions are being examined with adenosine A1, A2A, and A2B receptor knockout mice using the isolated perfused mouse heart preparation and isolated ventricular myocytes. Since these three subtypes can activate similar protein kinases, our working hypothesis is that receptor crosstalk optimizes these signaling mechanisms in specific subcellular fractions. Current studies are investigating adenosine receptor subtype modulation of protein kinases (PKC isoforms and mitogen activated protein kinases (MAPK)) and protein phosphatases in the plasma membrane and the subsarcolemmal pool of mitochondria.
In contrast to cardiac myocytes where the A1 receptor subtype exhibits the greatest expression, A2A and A2B receptors are expressed at much higher levels in cardiac fibroblasts. Studies in cultured cardiac fibroblasts from WT and KO mouse are examining the roles of these two receptor subtypes in the normal heart and in post-myocardial infarction (MI) hearts induced by permanent coronary artery occlusion. These studies are designed to determine the role of adenosine receptors in post-MI ventricular remodeling. Further studies are investigating adenosine receptor subtype modulation of -adrenergic receptor subtype induced increases in cardiac contractility and differences in -adrenergic receptor signaling in male and female hearts.