Adenosine receptors

The adenosine receptors are a class of G-protein coupled receptors with adenosine as endogenous ligand.

A1 adenosine receptor
The adenosine A1 receptor has been found to be ubiquitous throughout the entire body. This receptor has an inhibitory function on most of the tissues in which it rests. In the brain, it slows metabolic activity by a combination of actions. Presynaptically, it reduces vesicle release while post synaptically it has been found to stabilize the magnesium on the NMDA receptor.

Antagonism and Agonism
Caffeine, along with theophylline have been found to antagonize both A1 and A2a receptors in the brain. Specific antagonists include DPCPX, and CPT or CPX, while specific agonists include CPA.

A2A adenosine receptor
The A1 and A2a receptors of endogenous adenosine are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow[1]. Stimulation of the A1 receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing pacemaker cell function, resulting in a decrease in heart rate. This makes adenosine a useful medication for treating and diagnosing tachyarrhythmias, or excessively fast heart rates. This effect on the A1 receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid IV push during cardiac resuscitation. The rapid infusion causes a momentary myocardial stunning effect.

In comparison, the A2a receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. In normal physiological states, both of these receptors serve as protective mechanisms. However, in altered cardiac function, such as hypoperfusion caused by hypotension, heart attack or cardiac arrest caused by nonperfusing bradycardias, adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion.

Recent research on adenosine receptor function, and adenosine receptor antagonists such as theophylline has led to several randomized controlled trials using these receptor antagonists to treat bradyasystolic arrest. The primary researchers, TJ Mader et al at Tufts University School of Medicine, have reported some promising results.

Specific antagonists include KW6002 and SCH-58261, while specific agonists include CGS21680 and ATL-146e.

A3 adenosine receptor
It has been shown in studies to inhibit some specific signal pathways of adenosine. It allows for the inhibition of growth in human melanoma cells. Specific antagonists include MRS1191, MRS1523 and MRE3008F20, while specific agonists include Cl-IB-MECA and MRS3558.