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14-September-2008 18:02:41 - A1 receptor The correct title of this article is Adenosine A1 receptor. It appears incorrectly here because of technical restrictions. Adenosine A1 receptor Identifiers Symbols ADORA1; RDC7 External IDs OMIM: 102775 MGI: 99401 HomoloGene: 20165 Gene ontology Molecular function: rhodopsin-like receptor activity A1 adenosine receptor activity, G-protein coupled receptor activity Cellular component: integral to plasma membrane membrane Biological process: phagocytosis inflammatory response signal transduction G-protein coupled receptor protein signaling pathway cell-cell signaling nervous system development induction of apoptosis by extracellular signals RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 134 11539 Ensembl ENSG00000163485 ENSMUSG00000042429 Uniprot P30542 Q3URG8 Refseq NM_000674 mRNA NP_000665 protein NM_001008533 mRNA NP_001008533 protein Location Chr 1: 201.33 - 201.4 Mb Chr 1: 136.02 - 136.05 Mb Pubmed search 1 2 The adenosine A1 receptor1 is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as endogenous ligand. Contents 1 Biochemistry 2 Signaling 3 Mechanism 4 Antagonism and agonism 5 In heart 6 In neonatal medicine 7 References 8 External links Biochemistry A1 receptors are implicated in sleep promotion by inhibiting wake promoting cholinergic neurons in the basal forebrain.2 A1 receptors are also present in smooth muscle throughout the vascular system.3 The adenosine A1 receptor has been found to be ubiquitous throughout the entire body. Signaling Activation of the adenosine A1 receptor by an agonist causes binding of Gi1/2/3 or Go protein. Binding of Gi1/2/3 causes an inhibition of adenylate cyclase and therefore a decrease in the 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 phospholipase 2A Several types of potassium channels are activated but N-, P- and Q-type calcium channels are inhibited.4 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 antagonists include 8-Cyclopentyl-1,3-dipropylxanthine DPCPX, and Cyclopentyltheophylline CPT or 8-cyclopentyl-1,3-dipropylxanthine CPX, while specific agonists include 2-chloro-N6-cyclopentyladenosine CCPA. 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. 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. This makes adenosine a useful medication for treating and diagnosing tachyarrhythmias, or excessively fast heart rates. 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. 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 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. 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 A2 ARs. Thus, it may prove more advantageous to use selective A1 antagonists to help reduce adenosine-induced brain injury. References ^ Townsend-Nicholson A, Baker E, Schofield PR, Sutherland GR 1995. Localization of the adenosine A1 receptor subtype gene ADORA1 to chromosome 1q32.1. Genomics 26 2: 423-5. doi:10.1016/0888-75439580236-F. PMID 7601478. ^ Elmenhorst D, Meyer PT, Winz OH, Matusch A, Ermert J, Coenen HH, Basheer R, Haas HL, Zilles K, Bauer A 2007. Sleep deprivation increases A1 adenosine receptor binding in the human brain: a positron emission tomography study. J. Neurosci. 27 9: 2410-5. doi:10.1523/JNEUROSCI.5066-06.2007. PMID 17329439. ^ Tawfik HE, Schnermann J, Oldenburg PJ, Mustafa SJ 2005. Role of A1 adenosine receptors in regulation of vascular tone. Am. J. Physiol. Heart Circ. Physiol. 288 3: H1411-6. doi:10.1152/ajpheart.00684.2004. PMID 15539423. ^ 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. External links IUPHAR GPCR Database - A1 receptor MeSH Adenosine+A1+Receptor This transmembrane receptor-related article is a stub. v d e Transmembrane receptor: G protein-coupled receptors Class A: Rhodopsin like Adrenergic α1 A, B, D, α2 A, B, C, β1, β2, β3 Eicosanoid CysLT 1, 2, LTB4 1, 2, FPRL1, OXE, Prostaglandin DP, EP 1, 2, 3, 4, PGF, Prostacyclin, Thromboxane Neuropeptide B/W 1, 2, FF 1, 2, S, Y 1, 2, 4, 5 Orphan GPR 1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 79, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172, 173, 174, 176, 177, 182 Purinergics Adenosine A1, A2a, A2b, A3, P2Y, 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14 Serotonin all but 5-HT3 5-HT1 A, B, D, E, F, 5-HT2 A, B, C, 5-HT 4, 5A, 6, 7 Other Acetylcholine M1, M2, M3, M4, M5 - Adrenomedullin - Anaphylatoxin C3a, C5a - Angiotensin 1, 2 - Apelin - Bile acid - Bombesin BRS3, GRPR, NMBR - Bradykinin B1, B2 - Cannabinoid CB1, CB2 - Chemokine - Cholecystokinin A, B - Dopamine D1, D2, D3, D4, D5 - EBI2 - Endothelin A, B - Estrogen - Formyl peptide 1, L1, L2 - Free fatty acid 1, 2, 3, 4 - FSH - Galanin 1, 2, 3 - Gonadotropin-releasing hormone 1, 2 - Ghrelin - Histamine H1, H2, H3, H4 - Kisspeptin - Luteinizing hormone/choriogonadotropin - Lysophospholipid 1, 2, 3, 4, 5, 6, 7, 8 - MAS 1, 1L, D, E, F, G, X1, X2, X3, X4 - Melanocortin 1, 2, 3, 4, 5 - MCHR 1, 2 - Melatonin 1A, 1B- Motilin - neuromedin B, U 1, 2 - Neurotensin 1, 2 - Opioid Delta, Kappa, Mu, Nociceptin, but not Sigma - Olfactory - Opsin 3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH - Orexin 1, 2 - Oxytocin - Oxoglutarate - PAF - Prokineticin 1, 2 - Prolactin-releasing peptide - Protease-activated 1, 2, 3, 4 - Relaxin 1, 2, 3, 4 - Somatostatin 1, 2, 3, 4, 5 - SREB - Succinate - TAAR 1, 2, 3, 5, 6, 8, 9 - Tachykinin 1, 2, 3 - Thyrotropin - Thyrotropin-releasing hormone - Urotensin-II - Vasopressin 1A, 1B, 2 Class B: Secretin like Brain-specific angiogenesis inhibitor 1, 2, 3 - Cadherin 1, 2, 3 - Calcitonin - CD97 - Corticotropin-releasing hormone 1, 2 - EMR 1, 2, 3 - Glucagon GR, GIPR, GLP1R, GLP2R - Growth hormone releasing hormone - PACAPR1- GPR 56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157 - Latrophilin 1, 2, 3, ELTD1 - Parathyroid hormone 1, 2 - Secretin - Vasoactive intestinal peptide 1, 2 Class C: Metabotropic glutamate / pheromone Calcium-sensing receptor - GABA B 1, 2 - Glutamate receptor Metabotropic glutamate 1, 2, 3, 4, 5, 6, 7, 8 - GPRC6A - GPR 156, 158, 179 - RAIG 1, 2, 3, 4 - Taste receptors TAS1R 1, 2, 3 TAS2R 1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50 Frizzled / Smoothened Frizzled 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 - Smoothened Retrieved from http://en..org/wiki/Adenosine_A1_receptor Categories: Genes on chromosome 1 | Human proteins | Transmembrane receptor stubs | Adrenergic receptors | Signal transductionHidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 12 August 2008, at 15:34
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