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  • 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)
  • Because a characteristic of living beings is their ability to maintain a constant internal environment by self-adjusting physiological processes, homeostatic mechanisms are present at all levels of biological organisation, from simple cell mechanisms to the most complex mental functions. (scielo.br)
  • According to the main hypothesis suggested to account for this effect, the cause might be an altered regulation and/or response capacity of the physiological receptors involved in the drug action mechanisms. (scielo.br)
  • compounds
  • The present invention is directed to pyrazole, triazole and tetrazole compounds which are antagonists of orexin receptors. (patents.com)
  • The present invention is also directed to uses of the pyrazole, triazole, and tetrazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. (patents.com)
  • inhibition
  • 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)
  • 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)
  • Bailey MA (2004) Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors. (springer.com)
  • 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)
  • Adenosine caused inhibition of activation, cytokine production, metabolic activity, proliferation and ultimately effector differentiation of naive CD8 T cells. (uni-bielefeld.de)
  • tissue
  • 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)
  • These diseases strike from children to elderly and are generally characterized by progressive deterioration of cells, eventually leading to tissue or organ degeneration. (hindawi.com)
  • innate
  • Thus, regulating inflammatory mediators and reducing innate immune activation is a rational therapeutic strategy for MS. (jneurosci.org)
  • stimulation
  • 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)
  • 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)
  • We show that adenosine inhibited the initial activation of murine naive CD8 T cells after alpha CD3/CD28-mediated stimulation. (uni-bielefeld.de)
  • proinflammatory
  • Despite this more proinflammatory phenotype, A2AAR antagonist treatment still protected against EAE when A2AAR −/− lymphocytes were adoptively transferred to T cell-deficient A2AAR +/+ mice. (jimmunol.org)
  • Macrophages from A1AR -/- animals exhibited increased expression of the proinflammatory genes, interleukin-1β, and matrix metalloproteinase-12 on immune activation when matched with A1AR +/+ control cells. (jneurosci.org)
  • A2AR
  • 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)
  • Remarkably
  • Remarkably, A2AAR −/− donor hematopoietic cells potentiated severe EAE, whereas lack of A2AAR expression on nonhematopoietic cells protected against disease development. (jimmunol.org)
  • Remarkably, adenosine interfered efficiently with CD8 T-cell priming by professional antigen-presenting cells (dendritic cells) and semi-professional antigen-presenting cells (liver sinusoidal endothelial cells). (uni-bielefeld.de)
  • concentration
  • At normal doses, caffeine has variable effects on learning and memory, but it generally improves reaction time, wakefulness, concentration, and motor coordination. (wikipedia.org)
  • myocardial
  • 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)
  • tissues
  • Noncommunicable, neurological, and degenerative diseases are characterized by cell loss, ultimately leading to deterioration in quality or function of tissues or organs and possible failure of vital organs [ 1 ]. (hindawi.com)
  • 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)
  • pharmacological
  • 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)
  • hypersensitivity
  • However, its role in mast cell degranulation, which leads to hypersensitivity reactions in response to environmental factors, is not fully understood. (frontiersin.org)
  • Experimental evidence has shown that the rebound effect occurs at variable time intervals following the partial (e.g., dose change, receptor hypersensitivity, treatment initiation , tolerance etc.) or complete discontinuation of a drug, that the intensity of the ensuing symptoms is greater than that of the symptoms initially supressed by the drug, and that the duration of action varies. (scielo.br)
  • increases
  • The dominant effect of an elevation of plasma adenosine in the renal vasculature is an A 2A AR- and A 2B AR-mediated vasodilatation that increases global as well as medullary renal blood flow and is in part endothelium-dependent. (springer.com)
  • 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)
  • 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)
  • diseases
  • Regulatory T (T reg) cell deficiency causes lethal, CD4 + T cell-driven autoimmune diseases. (rupress.org)
  • Stem cell transplantation is used to treat these diseases, but this procedure is limited by the availability of a suitable donor. (rupress.org)
  • Although the etiology and pathogenesis of these diseases remain unclear, recent advances indicate that the processes of organ deterioration share common core features, including cell injury and dysfunction that contribute to functional and morphological impairment of cells. (hindawi.com)
  • The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved. (patents.com)
  • transporters
  • In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. (hindawi.com)
  • More specifically, the endothelial cells also possess transporters which show permeability characteristics and allow transport of oxygen and CO 2 across the BBB, bu these selectively prevent other substances from crossing [ 1 ]. (hindawi.com)
  • roles
  • Tumor necrosis factor alpha (TNF-α) was discovered more than a century ago, and its known roles have extended from within the immune system to include a neuro-inflammatory domain in the nervous system. (biomedcentral.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • found
  • These are quite different from other capillaries found in the body as their endothelial wall possesses tight junctions which obstruct transport between cells. (hindawi.com)
  • The adenosine A1 receptor has been found to be ubiquitous throughout the entire body. (wikipedia.org)
  • 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)
  • treatment
  • The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved. (patents.com)
  • severe
  • originator: GSK) is a 5-HT3 antagonist used for the management of severe diarrhea-predominant irritable bowel syndrome (IBS) in women only. (alsachim.com)
  • Remarkably, A2AAR −/− donor hematopoietic cells potentiated severe EAE, whereas lack of A2AAR expression on nonhematopoietic cells protected against disease development. (jimmunol.org)
  • heart
  • This makes adenosine a useful medication for treating and diagnosing tachyarrhythmias, or excessively fast heart rates. (wikipedia.org)
  • When it is administered intravenously, adenosine causes transient heart block in the atrioventricular (AV) node. (wikipedia.org)
  • When adenosine is used to cardiovert an abnormal rhythm, it is normal for the heart to enter ventricular asystole for a few seconds. (wikipedia.org)
  • function
  • This is not a fixed structure but its function depends on the complex interplay between the different cell types such as the endothelial cells, astrocytes, pericytes, and the extracellular matrix of the brain and blood flow maintained in the microvessels or brain capillaries. (hindawi.com)
  • During MS, infiltrating autoreactive immune cells attack and destroy myelin surrounding the axons of nerve cells in the brain and spinal cord, resulting in loss of neurologic function ( 9 ). (jimmunol.org)
  • brain
  • Furthermore, we demonstrate that in vivo CEST MRI is able to make a distinction between LS174T and U87 tumour cells implanted in the mouse brain. (regenerativemedicine.net)
  • Blood brain barrier (BBB) is a vasculature of the central nervous system (CNS) that is formed by capillary endothelial cells. (hindawi.com)
  • Thus, association of astrocytes with the brain endothelial cells provides a modular organization that allows precise control over the substances that enter or leave the brain. (hindawi.com)
  • It includes endothelial cells, astrocytes, and blood capillaries in the brain, which form the major structural component of the blood brain barrier. (hindawi.com)
  • In addition, blood capillaries in the brain are enclosed by the flattened "end-feet" of astrocytic cells, which also act as a partial, active barrier. (hindawi.com)
  • Caffeine (20 mg/kg) and KW60002 (3 mg/kg) given once daily for 6 days and on the 7th day 2 h before and 4 h after intrastriatal injection of LPS normalized the content of DA and its metabolites in both brain regions as well as decreased LPS-induced increase in the striatal level of hydroxyl radical. (biomedsearch.com)