• physiological
  • 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. (wikipedia.org)
  • tissue
  • Therefore, acute increases in extracellular adenosine levels tend to only have local and tissue-limited effects. (jimmunol.org)
  • Important clues to further understanding cancerous tissue protection from anti-tumor T cells have been provided by our recent insights into mechanisms of normal tissue protection from overactive immune cells [ 1 ]. (pubmedcentralcanada.ca)
  • In this role, A2AR functions similarly to programmed cell death-1 (PD-1) and cytotoxic t-lymphocyte associated protein-4 (CTLA-4) receptors, namely to suppress immunologic response and prevent associated tissue damage. (wikipedia.org)
  • A2AR
  • This may be now possible because of the recent demonstration that genetic deletion of immunosuppressive A2A and A2B adenosine receptors (A2AR and A2BR) or their pharmacological inactivation can prevent the inhibition of anti-tumor T cells by the hypoxic tumor microenvironment and as a result facilitate full tumor rejection [Ohta A, Gorelik E, Prasad SJ et al (2006) Proc Natl Acad Sci USA 103(35):13132- (pubmedcentralcanada.ca)
  • This approach is based on in vivo genetic evidence that A2AR play a critical role in the protection of normal tissues from overactive immune cells in acutely inflamed and hypoxic areas. (pubmedcentralcanada.ca)
  • The observations of much improved T-cell-mediated rejection of tumors in mice with inactivated A2AR strongly suggest that A2AR also protects hypoxic cancerous tissues and that A2AR should be inactivated in order to improve tumor rejection by anti-tumor T cells. (pubmedcentralcanada.ca)
  • While several A2A receptor antagonists have progressed to clinical trials for the treatment of Parkinson's disease, A2AR blockade in the context of cancer is less characterized. (wikipedia.org)
  • Mice treated with A2AR antagonists, such as ZM241385 (listed above) or caffeine, show significantly delayed tumor growth due to T-cells resistant to inhibition. (wikipedia.org)
  • coronary
  • As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. (wikipedia.org)
  • 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. (wikipedia.org)
  • The A1, together with A2A receptors of endogenous adenosine play a role in regulating myocardial oxygen consumption and coronary blood flow. (wikipedia.org)
  • This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments. (wikipedia.org)
  • The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. (wikipedia.org)
  • Other coronary arteries dilate when adenosine is administered while the segment past the occlusion is already maximally dilated. (wikipedia.org)
  • In the human heart, adenosine functions as an autacoid in the regulation of various cardiac functions such as heart rate, contractility, and coronary flow. (wikipedia.org)
  • theobromine
  • As a member of the xanthine family, it bears structural and pharmacological similarity to theobromine and caffeine, and is readily found in nature, and is present in tea (Camellia sinensis) and cocoa (Theobroma cacao). (wikipedia.org)
  • mice
  • In EAE induction experiments, A2AAR antagonist treatment protected mice from disease development and its associated CNS lymphocyte infiltration. (jimmunol.org)
  • The important role of T cells in cancer immunosurveillance is now strongly supported by genetic studies in mice [ 1 , 2 ] and human studies [ 3 - 5 ]. (pubmedcentralcanada.ca)
  • Why do anti-tumor T cells fail to completely and reliably destroy tumors in vivo even when the ability to recognize tumors is not the limiting factor and when very high numbers of highly lytic anti-tumor T cells are injected in a cancer patient [ 13 , 15 ] or tumor-bearing mice [ 16 ]? (pubmedcentralcanada.ca)
  • In a rodent models of PD, A 2A adenosine receptor antagonists increased locomotor activity in MPTP-treated or reserpinized mice, reversed haloperidol-induced catalepsy in rats (Shiozaki et al. (biomedsearch.com)
  • myocardial
  • 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. (wikipedia.org)
  • Adenosine is used as an adjunct to thallous (thallium) chloride TI 201 or Tc99m myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise. (wikipedia.org)
  • clinical
  • In addition, convincing data from clinical and animal studies have shown that the tumor microenvironment itself can suppress anti-tumor T cells [ 13 ]. (pubmedcentralcanada.ca)
  • inflammatory response
  • These results indicate that A2AAR expression on nonimmune cells (likely in the CNS) is required for efficient EAE development, while A2AAR lymphocyte expression is essential for limiting the severity of the inflammatory response. (jimmunol.org)
  • potential therapeutic
  • However the development of more highly selective A2A ligands has led towards other applications, with the most significant focus of research currently being the potential therapeutic role for A2A antagonists in the treatment of Parkinson's disease. (wikipedia.org)
  • responses
  • The application provides methods of treatment and prevention based on the long term effects of the compounds on T cell responses. (patents.com)
  • structurally
  • The crystallographic structure of the adenosine A2A receptor reveals a ligand binding pocket distinct from that of other structurally determined GPCRs (i.e., the beta-2 adrenergic receptor and rhodopsin). (wikipedia.org)
  • Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research. (wikipedia.org)
  • cardiac
  • Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function. (wikipedia.org)
  • 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. (wikipedia.org)
  • tumor
  • Cancer therapy by endogenous or adoptively transferred anti-tumor T cells is considered complementary to conventional cancer treatment by surgery, radiotherapy or chemotherapy. (pubmedcentralcanada.ca)
  • However, the scope of promising immunotherapeutic protocols is currently limited because tumors can create a 'hostile-immunosuppressive microenvironment that prevents their destruction by anti-tumor T cells. (pubmedcentralcanada.ca)
  • There is a possibility to develop better and more effective immunotherapies by inactivating mechanisms that inhibit anti-tumor T cells in the tumor microenvironment and thereby protect cancerous tissues from immune damage. (pubmedcentralcanada.ca)
  • Among recent advances in cancer immunology are reports of relatively successful adoptive T-cell therapy with selected forms of cancer [ 7 ] and better designs of cancer vaccines and treatments that improve the development of endogenous anti-tumor CD8 + T-cell effectors [ 8 - 12 ]. (pubmedcentralcanada.ca)
  • The long sought after explanation of the co-existence of tumors and of anti-tumor immune cells in a patient ('Hellstrom Paradox- [ 13 - 15 ] or in a mouse [ 16 ] has been a challenging problem to solve for more than 35 years. (pubmedcentralcanada.ca)
  • What is it in the tumor microenvironment in vivo that prevents tumor destruction by the tumor-specific and highly lytic in vitro anti-tumor CD8 + T cells? (pubmedcentralcanada.ca)
  • Some of the failures of adoptive therapy could be due to an inhibition of anti-tumor T cells by 'passenger-T suppressor cells [ 17 ] and/or by cytokines, which inhibit the development of the anti-tumor T cells [ 18 , 19 ]. (pubmedcentralcanada.ca)
  • Although substantial progress has been made in studying tumor escape from anti-tumor immune response [ 19 ], the mechanism of inhibition of lethal anti-tumor T cells in a poorly understood 'hostile-tumor microenvironment [ 13 - 16 ] is still perplexing. (pubmedcentralcanada.ca)
  • The puzzling inhibition of anti-tumor T cells in the tumor microenvironment provides yet another challenge [ 13 , 15 , 16 ]. (pubmedcentralcanada.ca)
  • reduces
  • Presynaptically, it reduces synaptic vesicle release while post synaptically it has been found to stabilize the magnesium on the NMDA receptor. (wikipedia.org)
  • Blockade
  • Studies have found that blockade of the A1 Receptor suppresses the osteoclast function, leading to increased bone density. (wikipedia.org)
  • typically
  • Fast rhythms of the heart that are confined to the atria (e.g., atrial fibrillation, atrial flutter) or ventricles (e.g., monomorphic ventricular tachycardia) and do not involve the AV node as part of the re-entrant circuit are not typically converted by adenosine. (wikipedia.org)
  • mechanism
  • Although originally developed as a folate antagonist for the treatment of cancer, its mechanism of action in the therapy of rheumatoid arthritis remains less clear. (aspetjournals.org)
  • cytokines
  • Hypercholesterolemia increases the levels of platelet activating factor (PAF) and cytokines which are known to stimulate granulocytes and endothelial cells to produce ROS. (tabsforsale24h.bid)
  • Pentoxifylline (PTX) is an inhibitor of cytokines and PAF and would reduce the generation of ROS by granulocytes and endothelial cells. (tabsforsale24h.bid)
  • lethal
  • Regulatory T (T reg) cell deficiency causes lethal, CD4 + T cell-driven autoimmune diseases. (rupress.org)
  • However pure powdered caffeine, which is available as a dietary supplement, can be lethal in tablespoon-sized amounts. (wikipedia.org)
  • lymphocytes
  • Although no defect in the suppressive ability of A2AAR −/− regulatory T cells was observed, A2AAR −/− lymphocytes were shown to proliferate more and produced more IFN-γ following stimulation. (jimmunol.org)