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Adenosine: what it is and what effects it has on the body

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In 1929, researchers Drury and Szent Gyorgyi demonstrated the actions of adenosine and bradycardia, focusing primarily on the cardiovascular system, but it was Feldberg and Sherwood who managed to demonstrate that the administration of adenosine at the cerebro-ventricular level could cause sedative effects, thus proposing that adenosine could be a neurotransmitter.

Adenosine is a nucleotide that is formed by the union of adenine with a ribose or ribofuranose ring via a β-N9 glycosidic bond, it should be noted that this nucleotide fulfills numerous functions of great importance for the organism (p. g., relevant roles in biochemical processes).

In this article we will talk about adenosine, and so that we can better understand what this nucleotide is, we will explain some of its functions in the organism and also the function of its receptors.

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What is adenosine?

What we know as adenosine is a nucleotide (which is an organic molecule) that is formed by the union of adenine (which is one of the 4 nitrogenous bases found in nucleic acids such as DNA and RNA) with a ribose or ribofuranose ring (known as 'RIB sugar' and is highly relevant to living beings) by means of a β-N9 glycosidic bond (responsible for linking one carbohydrate with another molecule; being in this case adenine with ribose).

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On the other hand, adenosine is an endogenous purine (nitrogenous base) that is synthesized by the degradation of some amino acids such as methionine, vain, threonine or isoleucine, as well as AMP (adenosine monophosphate).

It was the investigations of Sattin and Rall that demonstrated the actions of adenosine in the Central Nervous System (CNS) when they observed that this nucleotide could induce an increase in cyclic AMP (cAMP) in mammalian brain tissue slices, and also the methylxanthines were able to act as adenosine antagonists.

adenosine molecule

Later works, such as those by Snyder and his collaborators, confirmed the hypothesis that adenosine could exert actions modulators both in the processes at the biochemical level of the nervous tissue as well as in those other processes that were associated with the neurotransmission.

Other more recent investigations have developed the hypothesis about the relationship of the effect of some drugs with the activity of adenosine in the sympathetic nervous system, among which are the opiate derivatives and also the benzodiazepines.

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What is the function of adenosine in the body?

Adenosine is very important for the proper functioning of the body, since it plays a very important role in biochemical processes, such as the transfer of energy in the form of ATP (adenosine triphosphate, an essential nucleotide for the obtaining cellular energy) and ADP (adenosine disphosphate, a nucleotide that would be the non-phosphorylated part of the ATP).

Adenosine and adenine nucleotides (ADP, ATP and AMP), in addition to playing an important role in the correct functioning of the organism both at a biochemical and physiological level, including its participation in a wide diversity of cellular metabolic processes, also fulfills other functions, and that is that adenosine can exert modulatory actions both in the processes associated with neurotransmission as in those biochemical processes of the tissue highly strung.

It is important to highlight that the important function that adenosine plays as a neuromodulator within the central nervous system (CNS) is thanks to the interaction with its receptors known as Alpha1, Alpha2A, A2B and A3 that are distributed throughout the body in order to produce various processes such as bronchoconstriction, vasodilation or immunosuppression, among other functions.

Adenosine also has inhibitory and even sedative effects on neuronal activity. In fact, when caffeine manages to decrease sleep it is through the blockade of some adenosine receptor, since that it is adenosine that is responsible for increasing non-REM sleep (especially in phase IV) and also sleep REM. When a detuned adenosine inhibitor (deoxycoformycin) is applied, non-REM sleep is increased.

With regard to the role of adenosine in wakefulness, it is still early to give more conclusive results, since although it has been observed that they were at levels elevated adenosine A1 receptors after a night of nonREM sleep deprivation, it was also found that adenosine levels were not elevated after 48 hours of sleep deprivation. deprivation.

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The function of adenosine receptors

It is important to note that for the proper functioning of brain neurons to develop, the role played by adenosine is very important, since It is responsible for controlling cell proliferation and is also a mediator of inflammation.. In addition, adenosine receptors, known as "A2A", on the cell surface play an important role in carrying out those functions that we have just mentioned.

Likewise, adenosine receptors are responsible for regulating the immune, cardiovascular, and other major body systems; apart from being in charge of regulating the secretion of neurotransmitters. When activation of these adenosine A2A receptors occurs, it is when an activation of intracellular G proteins is induced and, immediately afterwards, the second messengers are activated.

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The role of adenosine receptors in addictions to psychostimulant substances

Adenosine snips (AR), are within the family of known G proteins that are found coupled to receptors and is made up of 4 members, known as receptors A1, A2A, A2B and A3. All these receptors are widely distributed, since they can be found throughout all the organs and tissues of the human body; Notably adenosine usually binds with higher affinity to A1 and A2A receptorsTherefore, most pharmacological actions are due to these two receptors.

On the other hand, the A1 and A2A receptors exert opposite actions at a biochemical level, and it is that while the A1 receptors manage to reduce the accumulation of AMPc (adenosine cyclic monophosphate) at the time of binding to the Gi/Go proteins, the A2As, are responsible for increasing the accumulation of cAMP in the cell cytoplasm because they are coupled to the Gs and Golf.

To date, researchers have been able to observe that these adenosine receptors participate in a wide variety of physiological responses, including inflammation, pain and also vasodilation, among other. Furthermore, within the central nervous system (CNS), A1 adenosine receptors are widely distributed throughout the cerebellum, hippocampus, and cortex; while the A2A receptors are fundamentally located in the olfactory bulb and in the striatum. Lastly, A2B and A3 receptors are normally found at low levels of expression.

On the other hand, in the field of psychopharmacology it has been discovered that adenosine, through the action of adenosine A1 and A2A receptors are capable of modulating antagonistic dopaminergic neurotransmission and thus reward systems. In addition, there are studies that support the hypothesis about the potential of A1 antagonists as a effective strategy to counteract the effects induced by substances psychostimulants.

There are also experimental studies that support the hypothesis that A2A/D2 heterodimers are partly responsible for reinforce the effects of those substances that have a psychostimulant powersuch as amphetamines or cocaine. In general, it has been possible to find results that are in favor of the hypothesis that the modulation excitatory A1 and A2A could be promising tools to counteract addiction to substances psychostimulants.

In relation to other stimulating substances, but in this case with a lower power of stimulation and, of course, less harmful to health such as those mentioned above, such as those of the methylxanthine group: theophylline (tea), caffeine (coffee) and theobromine (cocoa), it has been observed that its mechanism of action is through the inhibition of A1 and A2 receptors of adenosine. A1 receptors are responsible for mediating this inhibition that is exerted by adenosine on the release of neurotransmitters such as dopamine, acetylcholine or glutamate, among others.

When a person consumes caffeine, this substance blocks the A1 receptor, thus releasing the inhibitory effect of adenosine on neurotransmission. It is through this inhibitory control that adenosine exerts the mechanism by which caffeine, as well as other xanthines, are capable of enhancing alertness, concentration and attention both physiologically and psychological. Moreover, it has been observed that caffeine can increase the release of acetylcholine in the prefrontal cortex, also increasing activity at the cortical level.
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