The adenosine receptor system

Adenosine is a nucleoside, a chemical compound consisting of adenine (one of the four nucleic acid bases in human DNA) and a sugar molecule (β-D-ribose). It is an emergency molecule in the body. When the body finds itself in a stress situation, the heart muscle, for example, does not receive enough oxygen, as is the case with coronary heart disease, angina pectoris or myocardial infarction. The body releases adenosine and in this way tries to protect the heart tissue from major damage through various physiological processes.
Adenosine has its effect via four different adenosine receptors (A1, A2a, A2b, A3), which control signaling pathways involved in regulating many body functions, especially in the cardiovascular system. For example, activating A1 receptors protects the heart from oxygen deficiency and slows down the heart rate, while activation of the A2 receptors can improve the flow of blood to the heart and, in addition, lower blood pressure. Through these mechanisms, the adenosine-receptor signaling pathway also plays an important role in pathological developments in the heart.

Adenosine receptors offer researchers a starting point for developing new therapies. So-called receptor antagonists inhibit the effect of adenosine; agonists enhance or simulate the effect.

The difficulty when developing new active ingredients is that each adenosine receptor affects not just one, but a large number of body functions. For example, the A1 receptor plays a role in physiological processes not only in the heart, but also in the brain. Drugs that activate or inhibit adenosine receptors in a non-specific manner, or even act on several adenosine receptors at the same time, therefore involve a high risk of adverse side-effects. This problem can be solved by developing so-called partial agonists, which do not cause 100 percent activation of the receptors, like adenosine or full agonists do, but activate only a smaller percentage. In this way, not all the signals are triggered, but only those that can be used to treat a heart disease, for example.

Current research in heart diseases is therefore concentrating on the search for agonists that stimulate only specific adenosine receptors very selectively, without simultaneously also affecting other processes.

Bayer is researching in the field of the adenosine receptor system and working on the development of partial A1 agonists which selectively stimulate only specific adenosine receptors (for example, in the heart-muscle cells).