Adenosine Receptor - Pharmacology

Pharmacology

In humans, there are four types of adenosine receptors. Each is encoded by a separate gene and has different functions, although with some overlap. For instance, both A₁ receptors and A_2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A_2A receptor also has broader anti-inflammatory effects throughout the body. These two receptors also have important roles in the brain, regulating the release of other neurotransmitters such as dopamine and glutamate, while the A_2B and A₃ receptors are located mainly peripherally and are involved in processes such as inflammation and immune responses.

Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist adenosine being used in hospitals as treatment for severe tachycardia (rapid heart beat), and acting directly to slow the heart through action on all four adenosine receptors in heart tissue, as well as producing a sedative effect through action on A₁ and A_2A receptors in the brain. Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A₁ and A_2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate. These compounds also act as phosphodiesterase inhibitors, which produces additional anti-inflammatory effects, and makes them medically useful for the treatment of conditions such as asthma, but less suitable for use in scientific research.

Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research.