-
Pediatric Nursing 1991
Topics: Adenosine; Child; Drug Interactions; Humans; Pediatric Nursing
PubMed: 1754287
DOI: No ID Found -
Journal of Cellular Physiology Jan 2001Adenosine is an ubiquitous nucleoside present in all body cells. It is released from metabolically active or stressed cells and subsequently acts as a regulatory... (Review)
Review
Adenosine is an ubiquitous nucleoside present in all body cells. It is released from metabolically active or stressed cells and subsequently acts as a regulatory molecule through binding to specific A1, A2A, A2B and A3 cell surface receptors. The synthesis of agonists and antagonists to the adenosine receptors and their cloning enabled the exploration of their physiological functions. As nearly all cells express specific adenosine receptors, adenosine serves as a physiological regulator and acts as a cardioprotector, neuroprotector, chemoprotector, and as an immunomodulator. At the cellular level, activation of the receptors by adenosine initiates signal transduction mechanisms through G-protein associated receptors. Adenosine's unique characteristic is to differentially modulate normal and transformed cell growth, depending upon its extracellular concentration, the expression of adenosine cell surface receptors, and the physiological state of the target cell. Stimulation of cell proliferation following incubation with adenosine has been demonstrated in a variety of normal cells in the range of low micromolar concentrations, including mesangial and thymocyte cells, Swiss mouse 3T3 fibroblasts, and bone marrow cells. Induction of apoptosis in tumor or normal cells was shown at higher adenosine concentrations (>100 microM) such as in leukemia HL-60, lymphoma U-937, A431 epidermoid cells, and GH3 tumor pituitary cell lines. It was further noted that the A3 adenosine receptor (A3AR) plays a key role in the inhibitory and stimulatory growth activities of adenosine. Modulation of the A3AR was found to affect cell growth either positively or negatively depending on the concentration of the agonist, similar to the effect described for adenosine. At nanomolar concentrations, the A3AR agonists possess dual activity, i.e., antiproliferative activity toward tumor cells and stimulatory effect on bone marrow cells. In vivo, these agonists exerted anti-cancer effects, and when given in combination with chemotherapy, they enhanced the chemotherapeutic index and acted as chemoprotective agents. Taken together, activation of the A3AR, by minute concentrations of its natural ligand or synthetic agonists, may serve as a new approach for cancer therapy.
Topics: Adenosine; Animals; Cell Division; Humans; Neoplasms; Receptor, Adenosine A3; Receptors, Purinergic P1; Reference Values; Signal Transduction
PubMed: 11147810
DOI: 10.1002/1097-4652(200101)186:1<19::AID-JCP1011>3.0.CO;2-3 -
Deutsche Medizinische Wochenschrift... Dec 1993
Review
Topics: Adenine Nucleotides; Adenosine; Humans; Myocardium; Receptors, Purinergic P1
PubMed: 8269831
DOI: 10.1055/s-2008-1059524 -
Advanced Science (Weinheim,... May 2022The metabolite adenosine plays an important immunosuppressive role in the tumor microenvironment (TME) through its ligation with the metabolic checkpoint adenosine 2A...
The metabolite adenosine plays an important immunosuppressive role in the tumor microenvironment (TME) through its ligation with the metabolic checkpoint adenosine 2A receptor (A2AR). Here, an adenosine-A2AR negative feedback pathway is highlighted during photothermal-induced immunogenic cell death (ICD). Adenosine, hydrolyzed from ATP, is amplified during the photothermal-induced ICD process. It is possible to achieve a robust ICD-based immunotherapy via targeting the adenosine-A2AR metabolic pathway. In this regard, an A2AR inhibitor-loaded polydopamine nanocarrier masked by an acid-sensitive PEG shell is designed to enable tumor-specific delivery and photothermal-induced ICD simultaneously. Upon reaching the acidic TME, the PEG shell selectively detaches and exposes the adhesive polydopamine layer, causing the inhibitors to accumulate at the tumor tissue. The accumulated inhibitors attenuate adenosine's metabolically suppressive effect and strengthen the ICD immune response. It occurs through promoting dendritic cell (DC) activation, increasing CD8 T lymphocyte infiltration, and reducing the myeloid-derived suppressor cell (MDSC) population. Furthermore, this synergistic therapy significantly regresses the primary tumor, inhibits distal tumor growth, and prevents lung metastasis. The study highlights a strategy to enhance the immunotherapy efficacy of ICD by blocking the metabolic checkpoint A2AR using advanced nanomaterials.
Topics: Adenosine; Feedback; Humans; Immunotherapy; Metabolic Networks and Pathways; Neoplasms; Receptor, Adenosine A2A; Tumor Microenvironment
PubMed: 35306759
DOI: 10.1002/advs.202104182 -
Molecular Cell Jul 2016N(6)-methyladenosine (m(6)A) is a prevalent, reversible chemical modification of functional RNAs and is important for central events in biology. The core m(6)A writers...
N(6)-methyladenosine (m(6)A) is a prevalent, reversible chemical modification of functional RNAs and is important for central events in biology. The core m(6)A writers are Mettl3 and Mettl14, which both contain methyltransferase domains. How Mettl3 and Mettl14 cooperate to catalyze methylation of adenosines has remained elusive. We present crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. We determine that the heterodimeric complex of methyltransferase domains, combined with CCCH motifs, constitutes the minimally required regions for creating m(6)A modifications in vitro. We also show that Mettl3 is the catalytically active subunit, while Mettl14 plays a structural role critical for substrate recognition. Our model provides a molecular explanation for why certain mutations of Mettl3 and Mettl14 lead to impaired function of the methyltransferase complex.
Topics: Adenosine; Allosteric Regulation; Binding Sites; Catalytic Domain; HEK293 Cells; Humans; Methylation; Methyltransferases; Models, Molecular; Mutation; Protein Binding; Protein Conformation; RNA; S-Adenosylhomocysteine; S-Adenosylmethionine; Structure-Activity Relationship
PubMed: 27373337
DOI: 10.1016/j.molcel.2016.05.041 -
Tidsskrift For Den Norske Laegeforening... Mar 1998Adenosine consists of one ribose and one purine moiety and binds to specific receptors on cell membranes. The receptors are coupled to G-proteins and additionally to... (Review)
Review
Adenosine consists of one ribose and one purine moiety and binds to specific receptors on cell membranes. The receptors are coupled to G-proteins and additionally to various effector-systems. When a mismatch occurs between energy supply and energy demand, adenosine is produced by the catabolism of adenosine triphosphate. The metabolism of an organ is thereby coupled to the local blood supply (metabolic vasodilation). In addition to vasodilation, adenosine has several electrophysiological, cardioprotective, metabolic, and antiinflammatory properties. Adenosine is rapidly metabolized in blood and interstitial fluid, through cell absorption and degradation by adenosine deaminase. The short half-life of adenosine limits its clinical value. However, there are several ways of increasing the interstitial concentration of adenosine. At present, adenosine or adenosine-potentiating substances are used clinically to terminate supraventricular tachycardias, to induce myocardial ischemia in patients who are unable to exercise, and to reduce myocardial ischemia or reperfusion injury. Caffeine and other methylxanthines are adenosine receptor antagonists, and several of the pharmacodynamic properties of these substances are caused by adenosine receptor antagonism.
Topics: Adenosine; Caffeine; Humans; Myocardial Ischemia; Myocardial Reperfusion Injury; Receptors, Purinergic P1
PubMed: 9599504
DOI: No ID Found -
Kidney International Jun 1989Adenosine is known to decrease renal blood flow and glomerular filtration rate. We have tested the hypothesis that adenosine exerts contractile effects on mesangial...
Adenosine is known to decrease renal blood flow and glomerular filtration rate. We have tested the hypothesis that adenosine exerts contractile effects on mesangial cells. Furthermore, we have studied, using selective agonists and antagonists for adenosine, which kind of adenosine receptor, A1 or A2, is mainly implicated in this response. We also investigated whether calcium is involved in adenosine-induced mesangial cell contraction. Rat cultured mesangial cells were exposed to adenosine (10(-7) to 10(-3) M) and the contraction was measured as changes in planar cell surface area (PCSA). Adenosine induced a time- and dose-dependent reduction of PCSA. This reduction in PCSA was prevented by incubation with the A1 blocker PD116,948 but not with the A2 blocker PD115,199. Adenosine-5'-ethylcarboxamide (NECA), an A2 agonist, did not induce significant changes in PCSA whereas N6-S-1-methyl-2-phenylethyl adenosine (S-PIA), an A1 agonist, induced a dose-dependent decrease in PCSA. Adenosine-induced mesangial contraction was prevented by verapamil or by incubation in a calcium-free medium. These results suggest that adenosine induces a specific contraction of cultured rat mesangial cells that seems to be mediated by its binding to the adenosine A1-type receptor. This contraction seems to be dependent on the influx of extracellular calcium.
Topics: Adenosine; Animals; Calcium; Calcium Channel Blockers; Cells, Cultured; Glomerular Mesangium; Kinetics; Rats; Rats, Inbred Strains; Receptors, Purinergic
PubMed: 2770110
DOI: 10.1038/ki.1989.126 -
Molecules (Basel, Switzerland) Jan 2022Parahydrogen hyperpolarization has emerged as a promising tool for sensitivity-enhanced NMR metabolomics. It allows resolution and quantification of NMR signals of...
Parahydrogen hyperpolarization has emerged as a promising tool for sensitivity-enhanced NMR metabolomics. It allows resolution and quantification of NMR signals of certain classes of low-abundance metabolites that would otherwise be undetectable. Applications have been implemented in pharmacokinetics and doping drug detection, demonstrating the versatility of the technique. Yet, in order for the method to be adopted by the analytical community, certain limitations have to be understood and overcome. One such question is NMR signal assignment. At present, the only reliable way to establish the identity of an analyte that gives rise to certain parahydrogen hyperpolarized NMR signals is internal standard addition, which can be laborious. Herein we show that analogously to regular NMR metabolomics, generating libraries of hyperpolarized analyte signals is a viable way to address this limitation. We present hyperpolarized spectral data of adenosines and give an early example of identifying them from a urine sample with the small library. Doing so, we verify the detectability of a class of diagnostically valuable metabolites: adenosine and its derivatives, some of which are cancer biomarkers, and some are central to cellular energy management (e.g., ATP).
Topics: Adenosine; Humans; Hydrogen; Magnetic Resonance Spectroscopy; Metabolomics; Urine
PubMed: 35164066
DOI: 10.3390/molecules27030802 -
Circulation May 1991
Review
Topics: Adenosine; Dose-Response Relationship, Drug; Drug Interactions; Electrophysiology; Heart; Humans
PubMed: 2022011
DOI: 10.1161/01.cir.83.5.1499 -
Brain Research Mar 2016Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central...
Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central nervous system oxygen toxicity (CNS-OT), which greatly limits HBO's application. The regulation of astrocytes to the metabolism of adenosine is involved in epilepsy. In our study, we aimed to observe the effects of HBO exposure on the metabolism of adenosine in the brain. Furthermore, we aimed to confirm the possible mechanism underlying adenosine's mediation of the CNS-OT. Firstly, anesthetized rats exposed to 5 atm absolute HBO for 80 min. The concentrations of extracellular adenosine, ATP, ADP, and AMP were detected. Secondly, free-moving rats were exposed to HBO at the same pressure for 20 min, and the activities of 5'-nucleotidase and ADK in brain tissues were measured. For the mechanism studies, we observed the effects of a series of different doses of drugs related to adenosine metabolism on the latency of CNS-OT. Results showed HBO exposure could increase adenosine content by inhibiting ADK activity and improving 5'-nucleotidase activity. And adenosine metabolism during HBO exposure may be a protective response against HBO-induced CNS-OT. Moreover, the improvement of adenosine concentration, activation of adenosine A1R, or suppression of ADK and adenosine A2AR, which are involved in the prevention of HBO-induced CNS-OT. This is the first study to demonstrate HBO exposure regulated adenosine metabolism in the brain. Adenosine metabolism and adenosine receptors are related to HBO-induced CNS-OT development. These results will provide new potential targets for the termination or the attenuation of CNS-OT.
Topics: 5'-Nucleotidase; Adenosine; Animals; Astrocytes; Brain; Infusions, Intraventricular; Male; Oxygen; Rats; Rats, Sprague-Dawley
PubMed: 26806404
DOI: 10.1016/j.brainres.2016.01.026