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Adenosine is a key factor in regulating the body's sleep-wake cycle. [39] Adenosine levels rise during periods of wakefulness and lowers during sleep. Higher adenosine levels correlate with a stronger feeling of sleepiness , also known as sleep drive or sleep pressure. [ 40 ]
Caffeine keeps you awake by blocking adenosine receptors. Each type of adenosine receptor has different functions, although with some overlap. [3] For instance, both A 1 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. [4]
It also causes a negative dromotropic effect through the inhibition of AV-nodal conduction. [20] From the 1980s onwards, these effects of adenosine have been used in the treatment of patients with supraventricular tachycardia. [21] The regulation of vascular tone in the endothelium of blood vessels is mediated by purinergic signalling.
Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of the enzyme could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as anti-inflammatory agents. Alternative splicing results in two transcript variants encoding different isoforms.
Fatigue and sedation after heavy exertion can be caused by excess adenosine in the cells which signals muscle fiber to feel fatigued. In the brain, excess adenosine decreases alertness and causes sleepiness. In this way, adenosine may play a role in fatigue from MADD. [4] Recovery from over-exertion can be hours, days or even months.
Adenosine is a neuromodulator that is responsible for motor function, mood, memory, and learning. Its main purpose is the coordination of responses to different neurotransmitters. [5] Adenosine plays many important roles in biological systems, for example in the central nervous-, cardiovascular-, hepatic-, renal- and respiratory system.
The adenosine A2A receptor has also been shown to play a regulatory role in the adaptive immune system. In this role, it functions similarly to programmed cell death-1 (PD-1) and cytotoxic t-lymphocyte associated protein-4 ( CTLA-4 ) receptors, namely to suppress immunologic response and prevent associated tissue damage.
P1 receptors are preferentially activated by adenosine and P2Y receptors are preferentially more activated by ATP. P1 and P2Y receptors are known to be widely distributed in the brain, heart, kidneys, and adipose tissue. Xanthines (e.g. caffeine) specifically block adenosine receptors, and are known to induce a stimulating effect to one's behavior.