Adenosine: What It Is And What Effects It Has On The Body
In 1929, researchers Drury and Szent Gyorgyi demonstrated the actions of adenosine and bradycardia, focusing mainly 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 through a β-N9 glycosidic bond. It should be noted that this nucleotide fulfills numerous functions of great importance for the organism (e.g. , relevant functions 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 body and also the function of its receptors.
What we know as adenosine is a nucleotide (which is an organic molecule) which 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 ring of ribose or ribofuranose (known as ‘ RIB’ sugar and has a high relevance for living beings) through a β-N9 glycosidic bond (the one responsible for linking a carbohydrate with another molecule; in this case being adenine with ribose).
On the other hand, adenosine is an endogenous purine (nitrogen base) that is synthesized by the degradation of some amino acids such as methionine, sheath, threonine or isoleucine, as well as AMP (adenosine monophosphate).
It was the research 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 sections of mammalian brain tissue and in addition methylxanthines were able to act as antagonists of adenosine.
Later work, such as that of Snyder and his collaborators, confirmed the hypothesis that adenosine could exert modulating actions both in processes at the biochemical level of the nervous tissue as well as in those other processes that were associated with 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 opiate derivatives and also benzodiazepines.
What is the function of adenosine in the body?
Adenosine is very important for the proper functioning of the body, since plays a very relevant role in biochemical processes such as the transfer of energy in the form of ATP (adenosine triphosphate, an essential nucleotide for obtaining cellular energy) and ADP (adenosine disphosphate, a nucleotide that would be the unphosphorylated part of ATP).
Adenosine and adenine nucleotides (ADP, ATP and AMP), in addition to playing a relevant 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 modulating actions both in the processes associated with neurotransmission and in those biochemical processes of the nervous tissue.
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 Alfa1, Alfa2A, 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, in addition, has inhibitory and even sedative effects on neuronal activity In fact, when caffeine manages to reduce sleep, it is through blocking some adenosine receptor, since it is adenosine that is responsible for increasing non-REM sleep (especially in phase IV) and also REM sleep. When an inhibitor of detuned adenosine (deoxycoformycin) is applied, noREM sleep is increased.
With respect to the role of adenosine in wakefulness, it is still too early to give more conclusive results, since although it has been observed that adenosine A1 receptors were at elevated levels after a night of non-REM sleep deprivation, also It was found that adenosine levels were not elevated after 48 hours of deprivation.
It is important to highlight that for the proper functioning of brain neurons to develop, the role played by adenosine is very important, since it 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 a relevant 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 responsible for regulating the secretion of neurotransmitters. When activation of these A2A adenosine receptors occurs, it is when activation of intracellular G proteins is induced and, immediately afterwards, second messengers are activated
The role of adenosine receptors in addictions to psychostimulant substances
Adenosine (AR) cuts are found within the family of well-known G proteins that are coupled to receptors and are made up of 4 members, known as receptors A1, A2A, A2B and A3. All of these receptors are distributed very widely, since they can be found throughout all the organs and all the tissues of the human body; Notably adenosine usually binds with greater affinity to the A1 and A2A receptors so the majority of 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 while the A1 receptors manage to reduce the accumulation of cAMP (cyclic adenosine monophosphate) at the time of binding to the Gi/Go proteins, the A2A , are responsible for increasing the accumulation of cAMP in the cell cytoplasm because they are coupled to Gs and Golf.
To date, researchers have been able to observe that these adenosine receptors participate in a wide variety of responses at a physiological level, including inflammation, pain and also vasodilation, among other. Furthermore, within the central nervous system (CNS), adenosine A1 receptors are widely distributed throughout the cerebellum, hippocampus, and cortex; while A2A receptors are mainly located in the olfactory bulb and the striatum. Finally, 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 rewarding systems. Furthermore, there are studies that support the hypothesis about the potential of A1 antagonists as an effective strategy to counteract the effects induced by psychostimulant substances.
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 psychostimulant power, such as amphetamines or cocaine. In general, results have been found that are in favor of the hypothesis that the excitatory modulation of A1 and A2A could constitute promising tools to counteract addiction to psychostimulant substances.
In relation to other stimulant substances, but in this case with a lower stimulation power and, of course, less harmful to health like those previously mentioned, such as those from the methylxanthine group: theophylline (tea), caffeine (coffee) and theobromine (cocoa), it has been observed that its mechanism of action is through the inhibition of adenosine A1 and A2 receptors. The A1 receptors are responsible for mediating the 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 exerted by adenosine that the mechanism by which caffeine, as well as other xanthines, are capable of enhancing alertness, concentration and attention at both a physiological and psychological level. What’s more, it has been observed that caffeine can increase the release of acetylcholine in the prefrontal cortex, also increasing activity at the cortical level.
