The adenosine receptors (or P1 receptors[1]) are a class of purinergic receptors, G-protein coupled receptors with adenosine as endogenous ligand. Purinergic receptors are a family of newly characterized Plasma membrane molecules involved in several and as yet only partially known cellular functions such as vascular reactivity G protein-coupled receptors ( GPCRs) also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, and Adenosine is a Nucleoside composed of a Molecule of Adenine attached to a Ribose sugar molecule ( Ribofuranose) moiety via a β-N9- The word endogenous means "arising from within" the opposite of Exogenous. In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally [2]
In humans, there are four adenosine receptors. Each is encoded by a separate gene and has different functions, although also overlapping. For instance, both A1 receptors and A2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow. Myocardium is the muscular tissue of the Heart. Relationship to other layers The other tissues of the heart are the Endocardium Coronary circulation is the circulation of blood in the Blood vessels that supply Blood to and from the Heart muscle
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Comparison of subtypes
| Receptor | Gene | Mechanism [3] | Effects | Agonists | Antagonists |
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| A1 | ADORA1 | Gi/o --> cAMP↑/↓
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| A2A | ADORA2A | Gs --> cAMP↑ |
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| A2b | ADORA2B | Gs --> cAMP↑ |
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| A3 | ADORA3 | Gi/o --> |
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A1 adenosine receptor
The adenosine A1 receptor has been found to be ubiquitous throughout the entire body. The adenosine A1 receptor is one member of the Adenosine receptor group of G protein-coupled receptors with Adenosine as Endogenous Gi alpha subunit (or Gi/G0 or Gi protein) is a Heterotrimeric G protein subunit which inhibits the production of Cyclic adenosine monophosphate ( cAMP, cyclic AMP or 3'-5'-cyclic Adenosine monophosphate) is a Second messenger that is important in many biological The NMDA receptor ( NMDAR) is an Ionotropic receptor for Glutamate ( NMDA ( N -methyl D -aspartate is a name of its selective Measuring heart rate The Pulse rate (which in most people is identical to the heart rate can be measured at any point on the body where an Artery 's pulsation In Biochemistry, CCPA is 2-chloro-N(6-cyclopentyladenosine, a specific Receptor agonist for the Adenosine A1 receptor. Caffeine is a bitter white crystalline Xanthine Alkaloid that acts as a Psychoactive Stimulant Drug and a mild Diuretic Theophylline, also known as dimethylxanthine, is a Methylxanthine drug used in therapy for Respiratory diseases such as COPD or Asthma The adenosine A2A receptor, also known as ADORA2A, is an Adenosine receptor, but also denotes the human Gene encoding it The Gs alpha subunit (or Gs protein) is a Heterotrimeric G protein subunit which activates Adenylate cyclase. Cyclic adenosine monophosphate ( cAMP, cyclic AMP or 3'-5'-cyclic Adenosine monophosphate) is a Second messenger that is important in many biological Coronary circulation is the circulation of blood in the Blood vessels that supply Blood to and from the Heart muscle CGS21680 is a specific Adenosine A2A subtype receptor Agonist. Caffeine is a bitter white crystalline Xanthine Alkaloid that acts as a Psychoactive Stimulant Drug and a mild Diuretic Theophylline, also known as dimethylxanthine, is a Methylxanthine drug used in therapy for Respiratory diseases such as COPD or Asthma The adenosine A2b receptor, also known as ADORA2B, is an Adenosine receptor, and also denotes the human Gene incoding it The Gs alpha subunit (or Gs protein) is a Heterotrimeric G protein subunit which activates Adenylate cyclase. Cyclic adenosine monophosphate ( cAMP, cyclic AMP or 3'-5'-cyclic Adenosine monophosphate) is a Second messenger that is important in many biological The adenosine A3 receptor, also known as ADORA3, is an Adenosine receptor, but also denotes the human Gene encoding it Gi alpha subunit (or Gi/G0 or Gi protein) is a Heterotrimeric G protein subunit which inhibits the production of In Medicine, ischemia ( Greek ισχαιμία, isch- is restriction hema or haema is Blood) is a restriction Degranulation is a cellular process that releases Antimicrobial Cytotoxic molecules from secretory vesicles called granules found inside The adenosine A1 receptor is one member of the Adenosine receptor group of G protein-coupled receptors with Adenosine as Endogenous
Mechanism
This receptor has an inhibitory function on most of the tissues in which it rests. In the brain, it slows metabolic activity by a combination of actions. Presynaptically, it reduces synaptic vesicle release while post synaptically it has been found to stabilize the magnesium on the NMDA receptor. In a Neuron, synaptic vesicles, also called neurotransmitter vesicles, store the various Neurotransmitters that are released during Calcium -regulated The NMDA receptor ( NMDAR) is an Ionotropic receptor for Glutamate ( NMDA ( N -methyl D -aspartate is a name of its selective
Antagonism and agonism
Caffeine, along with theophylline have been found to antagonize both A1 and A2A receptors in the brain. Caffeine is a bitter white crystalline Xanthine Alkaloid that acts as a Psychoactive Stimulant Drug and a mild Diuretic Theophylline, also known as dimethylxanthine, is a Methylxanthine drug used in therapy for Respiratory diseases such as COPD or Asthma Specific antagonists include 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), and Cyclopentyltheophylline (CPT) or 8-cyclopentyl-1,3-dipropylxanthine (CPX), while specific agonists include 2-chloro-N(6)-cyclopentyladenosine (CCPA). A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks In Biochemistry, CCPA is 2-chloro-N(6-cyclopentyladenosine, a specific Receptor agonist for the Adenosine A1 receptor.
In heart
The A1, together with A2A receptors, of endogenous adenosine are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. Myocardium is the muscular tissue of the Heart. Relationship to other layers The other tissues of the heart are the Endocardium Stimulation of the A1 receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing pacemaker cell function, resulting in a decrease in heart rate. Measuring heart rate The Pulse rate (which in most people is identical to the heart rate can be measured at any point on the body where an Artery 's pulsation This makes adenosine a useful medication for treating and diagnosing tachyarrhythmias, or excessively fast heart rates. Dysrhythmia redirects here For the American band see Dysrhythmia (band. This effect on the A1 receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid IV push during cardiac resuscitation. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. The rapid infusion causes a momentary myocardial stunning effect.
In normal physiological states, this serves as protective mechanisms. However, in altered cardiac function, such as hypoperfusion caused by hypotension, heart attack or cardiac arrest caused by nonperfusing bradycardias, adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion. In Medicine, ischemia ( Greek ισχαιμία, isch- is restriction hema or haema is Blood) is a restriction In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply A cardiac arrest, also known as cardiorespiratory arrest, cardiopulmonary arrest or circulatory arrest, is the abrupt cessation of normal circulation of
In neonatal medicine
Adenosine antagonists are widely used in neonatal medicine;
Because a reduction in A1 expression appears to prevent hypoxia-induced ventriculomegaly and loss of white matter and therefore raise the possibility that pharmacological blockade of A1 may have clinical utility. Ventriculomegaly is a brain condition that occurs when the lateral ventricles become dilated
Theophylline and caffeine are nonselective adenosine antagonists that are used to stimulate respiration in premature infants.
However, we are unaware of clinical studies that have examined the incidence of periventricular leukomalacia (PVL) as related to neonatal caffeine use. Periventricular leukomalacia (PVL is characterized by the death of the White matter near the Cerebral ventricles due to softening of the brain tissue Caffeine may reduce cerebral blood flow in premature infants, possibly by blocking vascular A2 ARs. Thus, it may prove more advantageous to use selective A1 antagonists to help reduce adenosine-induced brain injury.
A2A adenosine receptor
As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. The adenosine A2A receptor, also known as ADORA2A, is an Adenosine receptor, but also denotes the human Gene encoding it
Mechanism
The activity of A2A adenosine receptor, a G-protein coupled receptor family member, is mediated by G proteins which activate adenylyl cyclase. It is abundant in basal ganglia, vasculature and platelets and it is a major target of caffeine. [4]
Function
The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. Coronary circulation is the circulation of blood in the Blood vessels that supply Blood to and from the Heart muscle Myocardium is the muscular tissue of the Heart. Relationship to other layers The other tissues of the heart are the Endocardium Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function.
Agonists and antagonists
Specific antagonists include KW6002 and SCH-58261, while specific agonists include CGS21680 and ATL-146e. CGS21680 is a specific Adenosine A2A subtype receptor Agonist. [5]
A2B adenosine receptor
This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. The adenosine A2b receptor, also known as ADORA2B, is an Adenosine receptor, and also denotes the human Gene incoding it This protein also interacts with netrin-1, which is involved in axon elongation.
A3 adenosine receptor
It has been shown in studies to inhibit some specific signal pathways of adenosine. The adenosine A3 receptor, also known as ADORA3, is an Adenosine receptor, but also denotes the human Gene encoding it It allows for the inhibition of growth in human melanoma cells. Specific antagonists include MRS1191, MRS1523 and MRE3008F20, while specific agonists include Cl-IB-MECA and MRS3558. The adenosine receptors (or P1 receptors) are a class of Purinergic receptors, G-protein coupled receptors with Adenosine as Endogenous [5]
References
- ^ Fredholm BB, Abbracchio MP, Burnstock G, Dubyak GR, Harden TK, Jacobson KA, Schwabe U, Williams M (1997). "Towards a revised nomenclature for P1 and P2 receptors". Trends Pharmacol. Sci. 18 (3): 79–82. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 9133776.
- ^ Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (2001). "International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors". Pharmacol. Rev. 53 (4): 527–52. PMID 11734617.
- ^ Unless else specified in boxes, then ref is:senselab
- ^ Entrez Gene: ADORA2A adenosine A2A receptor.
- ^ a b Jacobson KA, Gao ZG (2006). "Adenosine receptors as therapeutic targets". Nature reviews. Drug discovery 5 (3): 247–64. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16518376.
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