Adenosine

Adenosine is a nucleoside consisting of adenine attached to a ribose sugar. It is a component of RNA and a key product and regulator of cellular energy transfer, being part of ATP, ADP, and AMP. In addition to intracellular roles, adenosine also functions as an extracellular signaling molecule in many tissues.

Within cells, adenosine is produced from ATP during energy metabolism and is released into the extracellular space in response to stress or hypoxia. Extracellular adenosine is rapidly cleared by equilibrative nucleoside transporters into cells and by the enzyme adenosine deaminase to inosine, giving it a short half-life. It can be generated extracellularly from AMP by 5'-nucleotidase.

Adenosine signals through four G protein-coupled receptors, known as P1 or adenosine receptors: A1, A2A, A2B, and A3. Activation of A1 receptors tends to decrease heart rate and slow AV nodal conduction; A2A receptors promote vasodilation and modulate neurotransmission; A2B and A3 receptors have more variable, tissue-specific effects and can influence inflammatory responses. In the brain, adenosine acts as a neuromodulator and plays a major role in sleep regulation by promoting sleep onset and consolidation through A1 receptor activity.

Physiologically, extracellular adenosine influences myocardial blood flow, neuronal activity, and immune responses. It can affect airway tone and may provoke bronchoconstriction in susceptible individuals. Levels rise during hypoxia, signaling tissue to increase blood flow and limit injury.

Clinically, adenosine’s very short action makes it useful as a drug to terminate certain tachyarrhythmias, such as paroxysmal supraventricular tachycardia, by producing transient AV nodal block. It is also used in some pharmacologic stress tests. Caffeine and other xanthines antagonize adenosine receptors, illustrating its role as a neuromodulator.