A(3) adenosine receptor: a plausible therapeutic target for cardio-protection in diabetes.

Abstract

Diabetes mellitus categorized as type I and II, is a disease of pancreatic insulin, affecting blood glucose level in the body. Recent evidence suggests that cardiac diseases such as hypertension, coronary artery disease, congestive heart failure, and diabetic cardiomyopathy are associated with diabetes and hyperglycemia. The adenosine receptors (AR) have been reported to play an important role in the regulation of these diseases. Four adenosine receptors have been cloned and characterized from several different mammalian species. The receptors are named adenosine A(1), A(2A), A(2B), and A(3). The A(2A) and A(2B) receptors preferably interact with members of the Gs family of G proteins and the A(1) and A(3) receptors with Gi/o proteins. The ubiquitous levels of adenosine are found in each cell in normal conditions but in disease conditions its level has been shown to increase and activate G-protein mediated signaling pathway leading to artery constriction in cardiovascular diseases and diabetes. Various studies have demonstrated that A(3)AR is a potent cardioprotectant during myocardial ischemeia/ischemic reperfusion. Role of A(3)AR receptor as a possible cardioprotectant in diabetes is under investigation and studies have verified the involvement of cyclooxygenases (COXs) and NADPH oxidase pathways. This review summarizes the possible role of A(3)AR in cardiovascular disease and discusses advancement in the development of therapeutic agents targeting cardioprotection with discussion on recent patents on A(3) agonists that are being utilized in the clinical setting. We anticipate that detailed pharmacological studies of adenosine A(3) receptors could help in understanding the link between cardiovascular disease and diabetes and this can be utilized to develop newer therapies that selectively target A(3) receptor to overcome cardiac challenges.