China
Africa
Explore chapters and articles related to this topic
Local Stress-Limiting Systems and their Cardioprotective Effects
Published in Felix Z. Meerson, Alexander V. Galkin, Adaptive Protection of The Heart: Protecting Against Stress and Ischemic Damage, 2019
Felix Z. Meerson, Alexander V. Galkin
At the same time it is important to remember that adenosine not only modulates the regulation of the executive organs, but is also active in the central nervous system as well, where it is present at high concentrations and its receptors and binding sites are abundant in various brain regions: hippocampus, cerebellum, hypothalamus, etc.114,115,134 At present the adenosinergic system is regarded as a chief modulator of neuronal function. It mainly acts to impede neurotransmission by suppressing the release of neuromediators through the A1 and A2 receptors located on the axonal presynaptic membrane.113,114,127,140 Besides, neuronal inhibition by adenosine has also been observed at the postsynaptic membrane level.127,140 These data come from experiments with exogenous adenosine and its receptor agonists; however, convincing evidence is available that the same holds true for the endogenous mechanism (see Jackisch113 for references).
Overview of Neurotransmission: Relationship to the Action of Antiepileptic Drugs
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
Although adenosine can be taken up by synaptosomes and released following depolarization, there is no evidence that adenosine is stored in synaptic vesicles like the neurotransmitters we have considered above. Moreover, the release of adenosine appears to be calcium independent,120 although both calcium-dependent and calcium-independent release have apparently been reported.141 Unlike most established neurotransmitters, adenosine is apparently released from postsynaptic membranes, axons, and glial cells, in addition to nerve terminals.120 No clearcut adenosinergic pathways have been established in brain, although there is a regional variation in the concentration of adenosine and some adenosine-deaminase-rich neurons have been found in the basal hypothalamus.120 The pool from which adenosine is released on stimulation has not been identified.
Pharmacological Properties and Neurophsysiological Effects of Caffeine
Published in Barry D. Smith, Uma Gupta, B.S. Gupta, Caffeine and Activation Theory, 2006
In addition, A2a receptor KO mice have a tendency to escape more actively aversive situations than their wild-type controls (El Yacoubi et al., 2000a; Ledent et al., 1997). Similarly, adenosine A2a receptor antagonists increase mobility time in the forced swim test used in mice to test resignation and hence depressive behavior (Borsini, Lecci, Mancinelli, D’Aranno, & Meli, 1988; Duterte–Boucher, Leclère, Panissaud, & Costentin, 1988). Thus, adenosinergic mechanisms could be involved in symptoms of depression and adenosine A2a receptor antagonists might offer a novel approach to the treatment of depression.
Shaddock (Citrus maxima) peels extract restores cognitive function, cholinergic and purinergic enzyme systems in scopolamine-induced amnesic rats
Published in Drug and Chemical Toxicology, 2022
Ayokunle O. Ademosun, Adeniyi A. Adebayo, Temitope V. Popoola, Ganiyu Oboh
Adenosine deaminase (ADA) catalyzes the irreversible removal of amine group from adenosine to form inosine. In the purinergic system, ADA serves as an important point of regulation of adenosine level, a purine nucleoside that mediates diverse physiological conditions. Adenosine has been reported to play a neuromodulatory role in the CNS in mammals (Burnstock 2006, Burnstock et al.2011). In this study, it was observed that scopolamine administration increased the activity of ADA, and this effect was prevented by treatment with shaddock peels extract or donepezil. An increase in ADA activity increases the hydrolysis of adenosine to inosine. Thus, the effect of scopolamine on this enzyme leads to increased removal of extracellular adenosine decreasing its levels, which may lead to impairment of the adenosinergic neurotransmission. The depletion of extracellular adenosine can disrupt memory formation since adenosine has been reported as an important neuromodulator in synaptic plasticity (Burnstock et al.2011, Costa et al.2015, Akinyemi et al.2017). The decrease in ADA activity observed in the shaddock peel extract-treated group as shown in Figure 5 suggests possible mechanisms governing shaddock peel extract or donepezil action on cognitive function. This inhibitory effect on brain ADA activity would have a direct or indirect influence on the prevention of adenosine degradation in the CNS.
Amyloid beta (1–42) downregulates adenosine-2b receptors in addition to mitochondrial impairment and cholinergic dysfunction in memory-sensitive mouse brain regions
Published in Journal of Receptors and Signal Transduction, 2020
Bhupesh Chandra Semwal, Debapriya Garabadu
Adenosine is an endogenous purine nucleoside, formed from the metabolism of adenosine triphosphate (ATP) and exerts several functions in the brain through adenosinergic receptors [13]. Recently, caffeine, a nonselective adenosinergic drug, is reported to improve the cognitive function and reduce the Aβ aggregation in the AD-like animals [14,15]. It has also been documented that the adenosine receptor agonist exerts neuroprotection [16] and attenuates the mitochondrial oxidative stress by decreasing superoxide generation in experimental animals [17]. Additionally, it is reported that the activation of the A2b receptor exerts anti-inflammatory effect in the central nervous system of the animals [18,19]. However, there is no report about the involvement of A2b receptors in the pathophysiology of Aβ-induced AD-like manifestations.
Enhanced expression of CD39 and CD73 on T cells in the regulation of anti-tumor immune responses
Published in OncoImmunology, 2020
Ivan Shevchenko, Andreas Mathes, Christopher Groth, Svetlana Karakhanova, Verena Müller, Jochen Utikal, Jens Werner, Alexandr V. Bazhin, Viktor Umansky
Furthermore, we showed that tumor-infiltrating CD4+PD-1+ Tcon and CD8+PD-1+ T cells in mice contained distinctly higher frequencies of CD39+ cells compared to subsets lacking PD-1. These data are in line with the recent publications, demonstrating a higher expression of CD39 on CD8+PD-1+ T cells in mouse B16 melanoma17 as well as elevated CD73 expression on CD4+PD-1+ and CD8+PD-1+ T cells in mouse head and neck squamous cell carcinoma.33 This immune checkpoint receptor is upregulated in activated T cells and its interaction with ligands PD-L1 or PD-L2 expressed on tumor cells or MDSC represents a well-known mechanism of immune regulation.4 The simultaneous expression of CD39 and PD-1 in activated and tumor-infiltrating T cells suggests cooperation between the respective immunosuppressive pathways. In the tumor, where PD-1 ligands are often expressed at high levels on a variety of cells,4 PD-1 signaling is likely to augment the inhibitory effects of adenosine produced by T cells initially activated by tumor antigen. A number of treatment strategies targeting the PD-1 pathway have shown a significant clinical effect.9,30 Therefore, combining these therapies with anti-adenosinergic compounds could substantially improve their efficacy. This notion is supported by studies showing a synergistic beneficial effect of simultaneously targeting PD-1 and the A2a receptor in mouse tumor models.34,35