Adenosine receptors, role

Trincavelli ML, Tuscano D, Cecchetti P, Falleni A, Benzi L, Klotz K-N, Gremigni V, Cattabeni F, Lucacchini A, Martini C (2000) Agonist-induced internalization and recycling of the human A3 adenosine receptors role in receptor desensitization and resensitization. J Neurochem 75(4) 1493—1501... 

Extracellular adenosine acts through a class of G protein-coupled receptors (GPCRs), defined across mammalian species as Ab A2a, A2B, and A3ARs (adenosine receptors). Adenosine has a cytoprotective role in the body, both in the periphery and in the central nervous system. Following binding of adenosine, or another naturally occurring agonist, the receptor... 

Beyond Viagra, there are a number of other PDE inhibitors that are used clinically. In fact, the classic drugs papaverine and dipyridamole were used clinically before their effects on PDEs were known. Caffeine and theophylline (a compound found in tea) are also PDE inhibitors. However, all of these drugs most likely have multiple targets, making conclusions regarding the roles of PDEs in processes that are sensitive to these agents difficult to interpret. Certainly, some of their effects are due to their actions on adenosine receptors. 

Virus, R. M., Ticho, S., Pilditch, M. Radulovacki, M. (1990). A comparison of the effects of caffeine, 8-cyclopentyltheophylline, and alloxazine on sleep in rats. Possible roles of central nervous system adenosine receptors. Neuropsychopharmacology 3 (4), 243-9. 

In the 20 years since Daly reported the potential of adenosine receptors as drug targets (Daly, 1982), considerable advances have been made in the field of purinergic receptor-related research. Although a range of neurotransmitters is known, today there is no doubt that adenosine and adenosine 5 -triphosphate (ATP) also play an important role in the process of cell to cell communication. This function leads to multiple potential indications for research on adenosine and ATP, e.g. neurodegeneration or cardiovascular diseases, but here the focus lies on adenosine s role in pain (see also review by Salter and Sollevi, 2001). 

As mentioned above, a key factor in excluding a role for three out of the four recognised adenosine receptor subtypes was that the subtype selective agonists, CPA (Aj), CGS 21680 (A2A) and 2-CI-IB-MECA (A3), unlike the non-selective agonists,... 

Jacobson KA, Nikodijevic D, Shi D, Gallo-Rodriguez C, Olah ME, Stiles G, Daly JW (1993) A role for central Aj-adenosine receptors mediation of central depressant effects. FEBS Lett 336 57-60... 

Both the generation of mice overexpressing A3 adenosine receptors and targeted deletion of the A3 receptor gene have added important knowledge to the understanding of various functions of this adenosine receptor subtype. In particular its role in cardiovascular function was confirmed in numerous studies with genetically modified animals. 

The role of A3 adenosine receptors in modulating inflammatory responses was also confirmed in mice after its targeted deletion. Adenosine mediates an increase in cutaneous vascular permeability leading to extravasation of serum proteins as an important mechanism in the development of an inflammatory response. It turned out that this reaction is dependent on the presence of A3 adenosine receptors on mast cells as both A3 knockout mice and mice lacking mast cells showed no response (Tilley et al. 2000). Adenosine accomplishes mainly an anti-inflammatory effect which is generally assumed to be mediated by the A2A subtype (Sitkovsky et al. 2004). However, A3 agonists were also found to produce anti-inflammatory actions, for example by inhibiting neutrophil function. Such a contribution to inhibition of inflammation was recently confirmed in a comparison of A2A and A3 knockout mice (van der Hoeven et al. 2008). 

Liang BT, Jacobson KA (1998) A physiological role of the adenosine A receptor sustained car-dioprotection. Proc Natl Acad Sci U S A 95(12) 6995-6999 Linden J, Taylor HE, Robeva AS, Tucker AL, Stehle JH, Rivkees SA, Fink JS, Reppert SM (1993) Molecular cloning and functional expression of a sheep A3 adenosine receptor with widespread tissue distribution. Mol Pharmacol 44(3) 524—532 Londos C, Cooper DMF, Wolff J (1980) Subclasses of external adenosine receptors. Proc Natl Acad Sci U S A 77(5) 2551-2554... 

Ryzhov S, McCaleb JL, Goldstein AE, Biaggioni I (2007) Role of adenosine receptors in the regulation of angiogenic factos and neovascularization in hypoxia. J Pharmacol Exp Ther 320(2) 565-572... 

Recently, the therapeutic potential of stem cells engineered to release adenosine as a local source to augment endogenous adenosinergic functions was assayed in two cell transplantation experiments (Li et al. 2007, 2008 Boison 2008). Most of the studies about the role of adenosine as an anticonvulsant emphasize the preeminent involvement of A1 adenosine receptors. However, several studies using different experimental models of epilepsy have investigated the role of adenosine A2a and A3 receptors in this condition. 

Stella L, de Novellis V, Marabese I, Berrino L, Maione S, Filippelli A, Rossi F (1998) The role of A, adenosine receptors in central regulation of arterial blood pressure. Br J Pharmacol 125(3) 437-440... 

Yoon MH, Bae HB, Choi JI, Kim SJ, Chung ST, Kim CM (2006) Roles of adenosine receptor subtypes in the antinociceptive effect of intrathecal adenosine in a rat formalin test. Pharmacology 78(l) 21-26... 

Headrick JP, Willems L, Ashton KJ, Holmgren K, Peart J, Matherne GP (2003) Ischaemic tolerance in aged mouse myocardium the role of adenosine and effects of A( adenosine receptor overexpression. J Physiol 549(Pt 3) 823-833 Hein TW, Belardinelli L, Kuo L (1999) Adenosine A2a receptors mediate coronary microvascular dilation to adenosine role of nitric oxide and ATP-sensitive potassium channels. J Pharmacol Exp Ther 291(2) 655-664... 

Maddock HL, Broadley KJ, Bril A, Khandoudi N (2002b) Effects of adenosine receptor agonists on guinea-pig isolated working hearts and the role of endothelium and NO. J Pharm Pharmacol 54(6) 859-867... 

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