Adenosine receptor 737984 223056813 2008-07-02T11:12:17Z DOI bot 6652755 Citation maintenance. Removed redundant parameters. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. The '''adenosine receptors''' (or '''P1 receptors'''<ref name="pmid9133776">{{cite journal | author = Fredholm BB, Abbracchio MP, Burnstock G, Dubyak GR, Harden TK, Jacobson KA, Schwabe U, Williams M | title = Towards a revised nomenclature for P1 and P2 receptors | journal = Trends Pharmacol. Sci. | volume = 18 | issue = 3 | pages = 79–82 | year = 1997 | pmid = 9133776 | doi = 10.1016/S0165-6147(96)01038-3 }}</ref>) are a class of [[purinergic receptors]], [[G-protein coupled receptor]]s with [[adenosine]] as [[endogenous]] [[ligand]].<ref name="pmid11734617">{{cite journal | author = Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J | title = International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors | journal = Pharmacol. Rev. | volume = 53 | issue = 4 | pages = 527–52 | year = 2001 | pmid = 11734617 | doi = | issn = | url = http://pharmrev.aspetjournals.org/cgi/content/abstract/53/4/527 }}</ref> In humans, there are four adenosine receptors. Each is encoded by a separate gene and has different functions, although also overlapping. For instance, both A<sub>1</sub> receptors and A<sub>2A</sub> play roles in the heart, regulating [[myocardial]] oxygen consumption and [[coronary]] blood flow. ==Comparison of subtypes== {| class="wikitable" |+Adenosine receptors |- ! Receptor !! Gene !! Mechanism <ref> Unless else specified in boxes, then ref is:[http://senselab.med.yale.edu/NeuronDB/receptors2.asp#Neuropeptide%20Y%20receptors, senselab]</ref> !! Effects !! Agonists !! Antagonists |- ! '''[[Adenosine A1 receptor|A<sub>1</sub>]]''' | {{Gene|ADORA1}} || [[Gi alpha subunit|G<sub>i/o</sub>]] --> [[Cyclic adenosine monophosphate|cAMP]]&uarr;/&darr; * Inhibition **&darr; vesicle release **&darr; [[NMDA receptor]] activity || * decrease [[heart rate]] || *[[CCPA (biochemistry)|CCPA]] || *[[caffeine]] *[[theophylline]] *DPCPX *CPT *CPX |- ! '''[[Adenosine A2A receptor|A<sub>2A</sub>]]''' | {{Gene|ADORA2A}} || [[Gs alpha subunit|G<sub>s</sub>]] --> [[Cyclic adenosine monophosphate|cAMP]]&uarr; || * [[coronary circulation|coronary artery]] [[vasodilatation]] || *[[CGS21680]] *ATL-146e || *[[caffeine]] *[[theophylline]] *KW6002 *SCH-58261 |- ! '''[[Adenosine A2b receptor|A<sub>2b</sub>]]''' | {{Gene|ADORA2B}} || [[Gs alpha subunit|G<sub>s</sub>]] --> [[Cyclic adenosine monophosphate|cAMP]]&uarr; || || || *theophylline |- ! '''[[Adenosine A3 receptor|A<sub>3</sub>]]''' | {{Gene|ADORA3}} || [[Gi alpha subunit|G<sub>i/o</sub>]] --> || *cardioprotective in [[cardiac ischemia]] *inhibition of neutrophil [[degranulation]] || *Cl-IB-MECA *MRS3558 || *theophylline *MRS1191 *MRS1523 *MRE3008F20 |- |} ==A<sub>1</sub> adenosine receptor== {{Main|Adenosine A1 receptor}} The adenosine A<sub>1</sub> receptor has been found to be ubiquitous throughout the entire body. ===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]]. ===Antagonism and agonism=== [[Caffeine]], along with [[theophylline]] have been found to antagonize both A1 and A2A receptors in the brain. Specific [[receptor antagonist|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 (biochemistry)|CCPA]]). ===In the heart=== The A<sub>1</sub>, together with A<sub>2A</sub> receptors, of endogenous adenosine are believed to play a role in regulating [[myocardial]] oxygen consumption and coronary blood flow. Stimulation of the A<sub>1</sub> 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]]. This makes adenosine a useful medication for treating and diagnosing ''[[tachyarrhythmia]]s'', or excessively fast heart rates. This effect on the A<sub>1</sub> receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid [[intravenous|IV]] push during [[cardiac resuscitation]]. 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 bradycardia]]s, 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 neonatal medicine=== Adenosine antagonists are widely used in [[neonatal medicine]]; Because a reduction in A<sub>1</sub> expression appears to prevent hypoxia-induced [[ventriculomegaly]] and loss of white matter and therefore raise the possibility that pharmacological blockade of A<sub>1</sub> may have clinical utility. 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. Caffeine may reduce cerebral blood flow in premature infants, possibly by blocking vascular A<sub>2</sub> ARs. Thus, it may prove more advantageous to use selective A<sub>1</sub> antagonists to help reduce adenosine-induced brain injury. ==A<sub>2A</sub> adenosine receptor== {{Main|Adenosine A2A receptor}} As with the A<sub>1</sub>, the A<sub>2A</sub> receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. ===Mechanism=== The activity of A<sub>2A</sub> 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.<ref name="entrez">{{cite web | title = Entrez Gene: ADORA2A adenosine A2A receptor| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=135| accessdate = }}</ref> ===Function=== The A<sub>2A</sub> receptor is responsible for regulating myocardial blood flow by [[vasodilating]] the [[coronary circulation|coronary arteries]], which increases blood flow to the [[myocardium]], but may lead to hypotension. 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''.<ref name="pmid16518376">{{cite journal | author = Jacobson KA, Gao ZG | title = Adenosine receptors as therapeutic targets | journal = Nature reviews. Drug discovery | volume = 5 | issue = 3 | pages = 247–64 | year = 2006 | pmid = 16518376 | doi = 10.1038/nrd1983 }}</ref> ==A<sub>2B</sub> adenosine receptor== {{Main|Adenosine A2b receptor}} This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. ==A<sub>3</sub> adenosine receptor== {{Main|Adenosine A3 receptor}} It has been shown in studies to inhibit some specific signal pathways of adenosine. 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''.<ref name="pmid16518376" /> ==References == {{Reflist|2}} ==External links== *[http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1273 IUPHAR GPCR Database - Adenosine Receptors] *{{MeshName|Adenosine+Receptors}} {{G protein-coupled receptors}} [[Category:G protein coupled receptors]]