What is adenosine, the molecule of biochemical processes?

adenosina

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Many types of molecules, injected into the human body at the right dose and at the right time, can help relieve symptoms or even have seizures. Today, instead of talking about components that are already in our body, we will talk about one that is administered intravenously: adenosine.

Formed by several elements, this molecule can be of great help in certain circumstances, both for infants and adults. Let’s see what it consists of, the effects it causes in the organism and how to take advantage of them.

 

What is adenosine?

Adenosine is a nucleotide, the fundamental structure of nucleic acids. If we talk about DNA and RNA, we can surely locate ourselves better; nucleic acids are made up of nucleotides, which in turn make up our DNA and RNA. These are composed of a sugar molecule (ribose in RNA or deoxyribose in DNA) linked to a phosphate group and a nitrogenous base.

In the case of adenosine, it is formed by linking adenine (one of the 4 nitrogenous bases of nucleic acids) to a ribose or ribofuranose ring (essential for living organisms) by means of a β-N glycosidic bond. This linkage makes it possible for a carbohydrate to bind to another molecule (here, adenine with ribose). Adenosine is also an endogenous purine and therefore has a nitrogenous base that is synthesized by the degradation of certain amino acids (methionine, podine, threonine, isoleucine, AMP).

This molecule gained scientific importance when, in 1929, Drury and Szent Gyorgyi demonstrated the actions of adenosine and bradycardia (low heart rate), focusing on the cardiovascular system. However, it was Feldberg and Sherwood who demonstrated that the administration of adenosine at the cerebroventricular level had sedative effects. They were able to propose that adenosine was actually a neurotransmitter.

In spite of these fruitful and important researches, they were Sattin and Rall who demonstrated the actions of adenosine in the central nervous system (CNS). They were able to observe that this nucleotide induced an increase in cyclic Ampo in mammalian brain tissue slices. The methylxanthines also acted as adenosine antagonists.

Many subsequent works have been carried out such as those of Snyder and his team, which have made it possible to officially confirm that adenosine creates modulatory actions both in the biochemical processes of nervous tissue and in those associated with neurotransmission. Other more current research has developed a new hypothesis: the derivatives of opiates, benzodiazepines and other drugs have a strong relationship with adenosine activity in the sympathetic nervous system.

 

What is the function of adenosine?

What is adenosine, the molecule of biochemical processes - Ambar Lab

 

Adenosine performs a very important mission for the body to function properly. It is responsible for several biochemical processes, such as the transfer of energy in the form of adenosine triphosphate (ATP), essential for cellular energy, and adenosine disphosphate (ATP), the unphosphorylated part of ATP.

We need adenosine and its adenine nucleotides (ADP, ATP and AMP) for our body and that of many animals to function properly at both the biochemical and physiological levels. In addition to participating in many cellular metabolic processes, it exerts modulatory actions on neurotransmission-related processes and biochemical processes in nervous tissue.

It also performs a modulatory function in the CNS, interacting with Alpha1, Alpha2A, A2B and A3 receptors (distributed in the body to produce various processes such as bronchoconstriction, vasodilation or immunosuppression).

As if all these characteristics were not enough, it has also been discovered (we have briefly mentioned it before) that adenosine has inhibitory and sedative effects on neuronal activity. Let us explain this point with a practical example: when caffeine manages to reduce sleepiness, it is because it actually blocks some adenosine receptor. It may be the one that is responsible for increasing non-REM sleep or the one that controls REM sleep. If an inhibitor of detuned adenosine (deoxycoformycin) were applied in this state, non-REM sleep would be increased.

Para que nuestras neuronas cerebrales funcionen correctamente la adenosina debe cumplir su misión de controlar la a proliferación celular y de medir la inflamación. It is their receptors (A2A) that make it possible for all these functions to be carried out without any problems.

Its receptors also regulate the immune, cardiovascular and other major systems and the secretion of neurotransmitters. If the A2A receptors are activated, so are the intracellular G proteins and then the second messengers.

 

Adenosine receptors in psychostimulant addictions.

Adenosine trimers are within the G-protein family, which are coupled to receptors (A1, A2A, A2B and A3). These can be found in almost any part of the human body, from tissues to organs. This nucleotide usually binds more readily to A1 and A2A receptors.

These 2 receptors have opposite missions: A1 decreases cAMP accumulation when coupled to Gi/Go proteins and A2A increases it in the cell cytoplasm because they are coupled to Gs and Golf. These findings have led researchers to conclude that these receptors are involved in many physiological responses in the human body (inflammation, pain, vasodilation…). Adenosine A1 receptors within the CNS are distributed in the cerebellum, hippocampus and cortex; A2A receptors in the olfactory bulb and striatum; and A2B and A3 receptors are usually found at low levels of expression.

Within the field of psychopharmacology, adenosine has been found to be able to control antagonistic dopaminergic neurotransmission and reward systems (thanks to adenosine A1 and A2A receptors). Many studies confirm the possibility that A1 antagonists are an effective strategy to counteract the effects of psychostimulant substances.

Some experimental studies speak of hypotheses in which A2A/D2 heterodimers help to reinforce the effects of substances with psychostimulant power (amphetamines, cocaine…). Results have already been found in favor that excitatory modulation of A1 and A2A could be a new tool to counteract addiction to psychostimulant substances.

 

Precautions on adenosine administration

Although adenosine can bring enormous benefits to our body, like any other element, it should be treated with care and attention should be paid to its contraindications:

  • In patients with uncorrected hypovolemia, valvular stenosis, left-right shuntization, pericarditis or pericardial effusion, adenosine should be used with great caution (it can cause hypotension).
  • It should be used with caution in patients with atrial fibrillation or flutter, especially in those with an accessory pathway. They could develop an increase in driving.
  • Caution also in patients with recent heart transplantation (less than one year), since an increased sensitivity of the heart to this nucleotide has been observed.
  • Adenosine may precipitate or aggravate bronchospasm.
  • It should be used with caution in patients with a prolonged QT interval due to possible risk of detorsade de pointes.
  • Administration of the nucleotide in patients with a history of seizures should be closely monitored.
  • If angina, severe bradycardia, severe hypotension, respiratory failure or asystole/cardiac arrest are observed, adenosine administration should be discontinued immediately.

 

Use of adenosine

Adenosine can only be administered in a hospital setting, as electrocardiographic monitoring is required and cardiorespiratory resuscitation is available at any time if necessary. The doses for patients are:

  • Initial dose: 50-100 µg/kg (maximum dose: 6 mg).
  • Subsequent doses: if there is no response, a second dose of 200 µg/kg will be administered after 2 min. The process should be repeated up to a maximum of 0.5 mg/kg/dose in children or 0.3 mg/kg/dose in neonates or until sinus rhythm has been established (maximum: 12 mg/dose or 30 mg/total).
  • In perfusion (in pulmonary hypertension): 50 µg/kg/min with increments every 2 min up to 200 µg/kg/min or onset of symptoms. Further research is needed to confirm its usefulness with respect to this use.

 

adenosine - Ambar Lab

 

If the patient suffers from hepatic or renal insufficiency, it does not alter the efficacy of the treatment, since neither the liver nor the kidney participate in the degradation of adenosine. It should be prepared before use:

  • For doses lower than 600 µg, a dilution with physiological saline 0.9% or with 5% glucose saline up to a concentration of 300 µg/ml should be performed.

It can be administered peripherally or centrally, although the latter option is better. Choose a venous line as close as possible to the heart (avoid using those of the lower extremities). A quick injection is performed and the IV is immediately flushed with isotonic saline solution (5-10 ml). If there is no other remedy but to use a central line, the dose should be reduced by half.

Whenever you are in doubt about any type of molecule, ask your family doctor immediately. The nucleotide that is the subject of today’s article, for example, can only be administered in a hospital because it requires specific and special tools in case of problems.

If you have any questions about adenosine or any other nucleotide and want to know more or if there is a test to measure its levels, you can contact us. At Ambar Lab provide answers to all your needs, whether you are a hospital, a laboratory, a drug developer or a medical researcher.

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