What is adenosine, and where is it produced?
Adenosine is a nucleoside that has a signaling function. It is made of a purine linked to ribose sugar [1], and is produced in injured tissues. Cells suffering from a lack of blood supply or oxygen respond by releasing adenosine [2].
Adenosine forms in the catabolism of adenosine triphosphate, or ATP [1]. It can be produced in cells or outside of them, for example, in the brain [3].
In the heart, on the other hand, adenosine is predominantly produced in the cells [4].
Also, adenosine levels are high in areas where cells are under stress or dying, such as around solid tumors [5].
Adenosine can also be created artificially, in laboratories. It is produced by alkaline hydrolysis of ribonucleic acid from yeast, followed by adenosine extraction and purification by chromatographic separation [6].
How does adenosine influence sleep?
Adenosine acts as a sleep regulator. Its levels outside the cells rise during wakefulness and decrease in sleep [7, 8].
One way adenosine influences sleep is by inhibiting specific regions of the brain. For instance, it blocks the paraventricular hypothalamic nucleus, one of the key regions responsible for wakefulness, by binding to the type 1 adenosine receptors [9].
The same receptors are also found, and the same effect is in the cholinergic basal forebrain. This part of the central nervous system is pivotal for sleep induction [10].
Moreover, adenosine receptors type 2, found in the rostral forebrain in the subarachnoid space, may play a role in adenosine sleep promotion [10]. However, the impact of this mechanism on sleep needs more research.
Adenosine also indirectly impacts the circadian clock. Firstly, it accumulates in the brain during the waking period. The rising levels of adenosine in the brain increase tiredness [11].
Also, adenosine influences the expression of so-called clock genes. These genes, the Per1/2, are essential regulators of the circadian rhythm. By modulating genetic levels, adenosine influences the way external factors impact the day and night cycle [11].
Furthermore, adenosine modulates the pathways activated by light. It allows the body to optimize waking time according to the need for sleep, which is caused by the accumulation of adenosine [11].
Does adenosine make you tired?
Yes, increasing levels of adenosine lead to a gradual onset of tiredness. Generally speaking, adenosine has a hypnotic effect on the brain [12].
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How can you prevent the adenosine-caused tiredness?
To stop the feeling of tiredness caused by adenosine, drink coffee or green tea.
These beverages contain caffeine, which binds to the same receptors as adenosine. However, it does not activate adenosine receptors, rather it inhibits adenosine from binding to these receptors (for a limited time), and this prevents tiredness [13].
What happens if you have too much adenosine?
In situations where you have too much adenosine, you may experience side effects.
It occurs only when given an intravenous infusion or in abnormal health conditions, like heart attacks or brain trauma.
The symptoms of too high adenosine may include the cardiovascular system, the gastrointestinal, and the nervous systems.
However, adenosine is fast metabolized. Thus, the symptoms are short [14].
Among the side effects of adenosine are:
- lightheadedness [15],
- redness of the skin [15],
- skin flashes [15],
- nausea [15],
- nervousness [15],
- feeling of coming end [15],
- chest pain [16],
- chest pressure [16].
In severe cases, adenosine can lead to the development of cardiac arrhythmia, including premature atrial contractions and premature ventricular contractions, AV block, heart ischemia, low blood pressure, and prolonged asystole [15].
Also, neurological adverse symptoms can be severe. They may be blurred vision, severe headaches, acute numbness, and problems with speaking [16].
In rare cases, adenosine can lead to seizures and severe shortness of breath [16, 17].