Adenosine A1 receptor 4116762 224267487 2008-07-08T02:05:53Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. {{Wrongtitle|title=Adenosine A<sub>1</sub> receptor}} {{PBB|geneid=134}} The '''adenosine A<sub>1</sub> receptor'''<ref name="pmid7601478">{{cite journal | author = Townsend-Nicholson A, Baker E, Schofield PR, Sutherland GR | title = Localization of the adenosine A<sub>1</sub> receptor subtype gene (ADORA1) to chromosome 1q32.1 | journal = Genomics | volume = 26 | issue = 2 | pages = 423–5 | year = 1995 | pmid = 7601478 | doi = 10.1016/0888-7543(95)80236-F | issn = }}</ref> is one member of the [[adenosine receptor]] group of [[G protein-coupled]] receptors with [[adenosine]] as [[endogenous]] [[ligand]]. ==Biochemistry== A<sub>1</sub> receptors are implicated in sleep promotion by inhibiting wake promoting [[cholinergic]] neurons in the [[basal forebrain]].<ref name="pmid17329439">{{cite journal | author = Elmenhorst D, Meyer PT, Winz OH, Matusch A, Ermert J, Coenen HH, Basheer R, Haas HL, Zilles K, Bauer A | title = Sleep deprivation increases A<sub>1</sub> adenosine receptor binding in the human brain: a positron emission tomography study | journal = J. Neurosci. | volume = 27 | issue = 9 | pages = 2410–5 | year = 2007 | pmid = 17329439 | doi = 10.1523/JNEUROSCI.5066-06.2007 | issn = }}</ref> A<sub>1</sub> receptors are also present in smooth muscle throughout the vascular system.<ref name="pmid15539423">{{cite journal | author = Tawfik HE, Schnermann J, Oldenburg PJ, Mustafa SJ | title = Role of A<sub>1</sub> adenosine receptors in regulation of vascular tone | journal = Am. J. Physiol. Heart Circ. Physiol. | volume = 288 | issue = 3 | pages = H1411–6 | year = 2005 | pmid = 15539423 | doi = 10.1152/ajpheart.00684.2004 | issn = }}</ref> The adenosine A<sub>1</sub> receptor has been found to be ubiquitous throughout the entire body. ==Signaling== Activation of the adenosine A<sub>1</sub> receptor by an agonist causes binding of G<sub>i1/2/3</sub> or G<sub>o</sub> protein. Binding of G<sub>i1/2/3</sub> causes an inhibition of [[adenylate cyclase]] and therefore a decrease in the [[Cyclic_adenosine_monophosphate|cAMP]] concentration. An increase of the [[inositol triphosphate]]/[[diacylglycerol]] concentration is caused by an activation of [[phospholipase C]] while the elevated levels of [[arachidonic acid]] are mediated by [[PLA2|phospholipase 2A]] Several types of [[potassium channels]] are activated but N-, P- and Q-type [[calcium channels]] are inhibited.<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= |url=http://pharmrev.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11734617 }}</ref> ==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 A<sub>1</sub> and A<sub>2a</sub> receptors in the brain. Specific [[antagonist]]s 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 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. == References == {{Reflist}} ==External links== * [http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2166 IUPHAR GPCR Database - A<sub>1</sub> receptor] * {{MeshName|Adenosine+A1+Receptor}} {{transmembranereceptor-stub}} {{G protein-coupled receptors}} [[Category:Adrenergic receptors‎]] [[Category:Signal transduction]] <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> {{PBB_Controls | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = no | update_citations = no }}