Adenosine
Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building blocks of RNA (and its derivative deoxyadenosine is a building block of DNA), which are essential for all life. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. Adenosine is used as an intravenous medication for some cardiac arrhythmias.
adenosine
Certain SVTs can be successfully terminated with adenosine.[6] This includes any re-entrant arrhythmias that require the AV node for the re-entry, e.g., AV reentrant tachycardia (AVRT) and AV nodal reentrant tachycardia (AVNRT). In addition, atrial tachycardia can sometimes be terminated with adenosine.[7]
Fast rhythms of the heart that are confined to the atria (e.g., atrial fibrillation and atrial flutter) or ventricles (e.g., monomorphic ventricular tachycardia), and do not involve the AV node as part of the re-entrant circuit, are not typically converted by adenosine. However, the ventricular response rate is temporarily slowed with adenosine in such cases.[7]
Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V antiarrhythmic agent. When adenosine is used to cardiovert an abnormal rhythm, it is normal for the heart to enter ventricular asystole for a few seconds. This can be disconcerting to a normally conscious patient, and is associated with angina-like sensations in the chest.[8]
The recommended dose may be increased in patients on theophylline since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. The recommended dose is also reduced by half in patients presenting congestive heart failure, myocardial infarction, shock, hypoxia, and/or chronic liver disease or chronic kidney disease, and in elderly patients.
Methylxanthines (e.g. caffeine found in coffee, theophylline found in tea, or theobromine found in chocolate) have a purine structure and bind to some of the same receptors as adenosine.[12] Methylxanthines act as competitive antagonists of adenosine and can blunt its pharmacological effects.[13] Individuals taking large quantities of methylxanthines may require increased doses of adenosine.
Caffeine acts by blocking binding of adenosine to the adenosine A1 receptor, which enhances release of the neurotransmitter acetylcholine.[14] Caffeine also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase.[15] "Caffeine has a three-dimensional structure similar to that of adenosine," which allows it to bind and block its receptors.[16]
Adenosine is an endogenous purine nucleoside that modulates many physiological processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3).[18]
All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclase activity. The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates adenylate cyclase activity. In addition, A1 receptors couple to Go, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gq and stimulate phospholipase activity.Researchers at Cornell University have recently shown adenosine receptors to be key in opening the blood-brain barrier (BBB).Mice dosed with adenosine have shown increased transport across the BBB of amyloid plaque antibodies and prodrugs associated with Parkinson's disease, Alzheimer's, multiple sclerosis, and cancers of the central nervous system.[23]
Adenosine is an endogenous agonist of the ghrelin/growth hormone secretagogue receptor.[24] However, while it is able to increase appetite, unlike other agonists of this receptor, adenosine is unable to induce the secretion of growth hormone and increase its plasma levels.[24]
When it is administered intravenously, adenosine causes transient heart block in the atrioventricular (AV) node. This is mediated via the A1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K+ efflux via inward rectifier K+ channels, subsequently inhibiting Ca2+ current.[25][26] It also causes endothelial-dependent relaxation of smooth muscle as is found inside the artery walls. This causes dilation of the "normal" segments of arteries, i.e. where the endothelium is not separated from the tunica media by atherosclerotic plaque. This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments.
The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. Other coronary arteries dilate when adenosine is administered while the segment past the occlusion is already maximally dilated, which is a process called coronary steal. This leads to less blood reaching the ischemic tissue, which in turn produces the characteristic chest pain.
The adenosine analog NITD008 has been reported to directly inhibit the recombinant RNA-dependent RNA polymerase of the dengue virus by terminating its RNA chain synthesis. This interaction suppresses peak viremia and rise in cytokines and prevents lethality in infected animals, raising the possibility of a new treatment for this flavivirus.[28] The 7-deaza-adenosine analog has been shown to inhibit the replication of the hepatitis C virus.[29] BCX4430 is protective against Ebola and Marburg viruses.[30] Such adenosine analogs are potentially clinically useful since they can be taken orally.
Adenosine is believed to be an anti-inflammatory agent at the A2A receptor.[31][32] Topical treatment of adenosine to foot wounds in diabetes mellitus has been shown in lab animals to drastically increase tissue repair and reconstruction. Topical administration of adenosine for use in wound-healing deficiencies and diabetes mellitus in humans is currently under clinical investigation.
In general, adenosine has an inhibitory effect in the central nervous system (CNS).Caffeine's stimulatory effects are credited primarily (although not entirely) to its capacity to block adenosine receptors, thereby reducing the inhibitory tonus of adenosine in the CNS. This reduction in adenosine activity leads to increased activity of the neurotransmitters dopamine and glutamate.[34] Experimental evidence suggests that adenosine and adenosine agonists can activate Trk receptor phosphorylation through a mechanism that requires the adenosine A2A receptor.[35]
The principal component of cannabis delta-9-tetrahydrocannabinol (THC) and the endocannabinoid anandamide (AEA) induce sleep in rats by increasing adenosine levels in the basal forebrain. They also significantly increase slow-wave sleep during the third hour, mediated by CB1 receptor activation. These findings identify a potential therapeutic use of cannabinoids to induce sleep in conditions where sleep may be severely attenuated.[39]
As the body uses energy, the brain produces adenosine, a chemical compound that influences the need to sleep Trusted Source National Institute of Neurological Disorders and Stroke (NINDS) NINDS aims to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. View Source . Adenosine is also available as a prescription drug Trusted Source National Center for Biotechnology Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source , primarily used to treat irregular or fast heartbeats. Because adenosine receptors are found in multiple bodily systems, this chemical can affect the entire body. We explore the role adenosine plays in the human body, particularly in regards to sleep.
Adenosine is a neurotransmitter Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source naturally found in the human body. Cells in the nervous system use neurotransmitters to transmit information Trusted Source Medline Plus MedlinePlus is an online health information resource for patients and their families and friends. View Source among cells. Adenosine receptors are part of this chemical process Trusted Source National Institute of Neurological Disorders and Stroke (NINDS) NINDS aims to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. View Source , allowing adenosine to enter a cell and stimulate changes that enable the body to act out certain biological functions.
When taken as a medication, adenosine can reduce heart rate and help manage irregular heartbeats. The administration of adenosine can reduce pain Trusted Source National Center for Biotechnology Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source and lower blood pressure, especially in people undergoing surgery. In addition to being used as a treatment, adenosine may be given during a cardiac stress test to help medical professionals make heart-related diagnoses.
This relationship between ATP and adenosine is one mechanism through which increased activity leads to tiredness. The front of the brain, called the basal forebrain, releases adenosine as energy is used, increasing the need for sleep. Then, sleep likely allows the adenosine that has been accumulating throughout the day to clear out of the brain Trusted Source UpToDate More than 2 million healthcare providers around the world choose UpToDate to help make appropriate care decisions and drive better health outcomes. UpToDate delivers evidence-based clinical decision support that is clear, actionable, and rich with real-world insights. View Source . Experts also suspect that the presence of adenosine helps prompt the deepest stage of sleep. 041b061a72