Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of group 2- versus group 3-selective metabotropic glutamate (mGlu) receptor agonists were examined against forskolin (10 microM)-, vasoactive intestinal peptide (VIP; 1 microM)- and 5'-N-ethylcarboxamidoadenosine (NECA; 10 microM)-stimulated cAMP accumulations in adult rat hippocampal slices (in the presence of adenosine deaminase). Group 2 mGlu receptor-selective ((1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD) and (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (L-CCG I)) and group 3 mGlu receptor-selective (L-2-amino-4-phosphonobutyric acid (L-AP4) and L-serine-O-phosphate) agonists greatly inhibited forskolin-stimulated cAMP formation ( > 80% at maximally effective concentrations). In contrast, stimulation of cAMP by VIP or NECA was inhibited by group 3, but not by group 2, mGlu receptor agonists. In fact, group 2 mGlu receptor agonists greatly potentiated cAMP accumulation evoked by NECA. Both the inhibitory effects of 1S,3R-ACPD on forskolin-stimulated cAMP and the potentiating effects on NECA-stimulated cAMP accumulation were reversed by the competitive group 1/2 mGlu receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG). However, (+)-MCPG had no effects on L-AP4 inhibition of cAMP. Thus, the effects of group 2 versus group 3 mGlu receptor agonists on cAMP coupling can be pharmacologically as well as functionally differentiated in the rat hippocampus.
...
PMID:Differentiation of group 2 and group 3 metabotropic glutamate receptor cAMP responses in the rat hippocampus. 866 60

Carotid blood flow in rats was measured by implanted transit-time ultrasonic flowprobes throughout hyperbaric experiments conducted up to 70 bar (7 MPa) with a helium-oxygen hyperoxic (PO2 = 400 mbar) mixture. Before the hyperbaric experiment, an intracerebroventricular (ICV) injection of phosphate saline-buffered solution (PBS) or adenosine deaminase (ADA, 100 U.ml-1) in PBS was performed. Throughout the hyperbaric experiment carotid blood flow increased with ambiant pressure in PBS-treated rats. Conversely, the increase in carotid blood flow was attenuated by ADA treatment. These results suggest that the increase in carotid blood flow at high ambiant pressure could result from an increase of adenosine concentration in the rat brain.
...
PMID:Central inhibitory effect of adenosine deaminase on carotid blood flow increase at high pressure. 883 7

Using the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), we determine the contribution of the adenosine pathway to the abundant purine release of two Langendroff-perfused rat heart models which differ particularly in inorganic phosphate (Pi) content: the 2-deoxy-D-glucose (2DG) perfused heart and the anoxic heart. We measure the release of coronary purines by high performance liquid chromatography, and the content of myocardial metabolites by 31P nuclear magnetic resonance spectroscopy. In the 2DG-perfused heart (2 mM for 45 min), the release of inosine [130 nmol/(min.gww)] is much larger than that of adenosine, and EHNA (50 microM) has little effect, showing that the pathway of inosine monophosphate (IMP) accounts for 97% of purine catabolism. In the anoxic heart (100% N2 for 45 min), where inosine and adenosine release are comparable in the absence of EHNA, the inhibitor reduces the release of inosine and catabolites from 50 to 20 nmol/(min.gww) and increases that of adenosine [from 30 to 55 nmol/(min.gww)], showing that the contributions of the IMP and adenosine pathways are 23 and 77%. The difference between the two models has been ascribed to the inhibition of AMP deaminase by Pi in the anoxic heart (Chen W, et al., 1996). We discuss the physiological significance of this heart-specific duality of degradation pathways.
...
PMID:AMP degradation in the perfused rat heart during 2-deoxy-D-glucose perfusion and anoxia. Part II: The determination of the degradation pathways using an adenosine deaminase inhibitor. 893 Aug 12

ATP and ADP are simultaneously released from activated platelets in equimolar concentrations. Micromolar concentrations of ATP inhibit platelet aggregation by both competitive and non-competitive mechanisms. The current studies addressed the question of how platelets respond to agonists in the presence of nanomolar and micromolar concentrations of ATP and ADP alone or in combination. This is a significant issue since the concentration of ATP +/- ADP may vary widely within a microenvironment depending upon the source and cause for the release of the nucleotides. ATP (1-10 nM) was found to significantly enhance the thromboxane A2 analog, U44619-, collagen- and thrombin-induced platelet aggregations. Conversely, ATP at 1-100 microM inhibited these same reactions. ADP, in general, behaved exactly opposite to ATP. When equal amounts of ATP and ADP were added together the ADP response appeared to predominate. The observed ATP-induced response was not due to a hydrolytic product as evidenced by an unaltered response to ATP in the presence of adenosine deaminase or the ATP generating system, creatine phosphate plus creatine phosphokinase. Adenosine (1-10 nM), like ADP, inhibited agonist-induced platelet aggregation. The stimulation of agonist-induced platelet aggregation by 1-10 nM extracellular ATP appears to depend upon the phosphorylation of platelet membrane ecto proteins. The ATP analog, beta gamma-methylene ATP, that is incapable of serving as a phosphate donor for protein kinases, inhibited rather than stimulated agonist-induced platelet aggregation. The dual response of platelets to low and high concentrations of extracellular ATP +/- ADP may play a physiological role in hemostasis and thrombosis under normal and pathological conditions.
...
PMID:A possible dual physiological role of extracellular ATP in the modulation of platelet aggregation. 904 33

During moderate but nevertheless prolonged myocardial ischemia, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". Short-term hibernating myocardium can respond to an inotropic stimulation with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. This situation of an increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. A role for endogenous adenosine in the development of hibernation has been excluded, since neither contractile function nor metabolic parameters nor viability are altered by increased catabolism of endogenous adenosine by infusion of adenosine deaminase. Whereas short-term hibernation is well characterized in animal experiments, the existence of hibernation over weeks or months (long-term hibernation) can only be inferred from clinical studies. Hibernation, as defined by Rahimtoola, is a state of chronic contractile dysfunction in patients with coronary artery disease which is fully reversible upon reperfusion.
...
PMID:[Hibernating myocardium: no involvement of endogenous adenosine]. 906 63

The objective of the present study was to establish the optimal combination of inhibitors of adenosine metabolism and nucleotide precursors resulting in long-term increase in endogenous adenosine concentration without adverse metabolic consequences in non-ischemic cardiomyocytes and endothelial cells. Cardiomyocytes and endothelial cells were isolated after collagenase digestion of the rat heart. Freshly isolated cardiac myocytes or cultured endothelial cells were incubated for up to 8 h with no inhibitors or substrates or with various combinations of adenosine deaminase inhibitor: 5 micron M erythro-9(2-hydroxy-3-nonyl)adenine (EHNA), adenosine kinase inhibitors: 10 micro M 5'-iodotubercidin (ITu) or 10 micro M 5'-aminoadenosine (AA) and nucleotide precursors: 100 micro M adenine, 2.5 mm ribose and 5 mm inorganic phosphate. Nucleotide, nucleoside and base concentrations were evaluated at the end of the incubation by HPLC in cardiomyocyte or endothelial cells extracts and in incubation media. Adenosine content in cardiomyocyte suspension was enhanced after 3 h incubation in the presence of ITu+EHNA as compared to EHNA alone (2.8+/-0.2 v 0.9+/-0.2 nmol/mg protein, respectively). ATP decreased from an initial value of 22.7+/-0.7 nmol/mg protein to 18.9+/-0.7 in the presence of ITu+EHNA, while ATP was maintained at 21.8+/-0.7 nmol/mg protein with EHNA. With adenine+ITu+EHNA, the changes were similar to those observed with ITu+EHNA. However, with ribose+adenine+ITu+EHNA, ATP increased to 25. 8+/-1.2 nmol/mg protein and adenosine concentration was elevated to 3.9+/-0.3 nmol/mg protein. Similar results were observed if AA was used instead of ITu to inhibit adenosine kinase. All the changes were maintained after 8 h of incubation. Adenosine content was increased in endothelial cells incubated with ITu+EHNA to 3.1+/-0.4 nmol/mg protein as compared to 1.1+/-0.2 nmol/mg protein with EHNA alone after 3 h, while ATP decreased (18.1+/-1.1 v 22.0+/-1.4 nmol/mg protein with EHNA+ITu or EHNA, respectively). In the presence of adenine+ITu+EHNA, adenosine content increased after 3 h to 6.5+/-0.9 nmol/mg protein while ATP was elevated to 26.1+/-0.8 nmol/mg protein. Additional presence of ribose was without effect. No changes in adenylate energy charge were observed in cardiomyocytes or endothelium under any conditions studied. Inhibition of adenosine kinase and adenosine deaminase caused a decrease in ATP together with increased adenosine content both in endothelial cells and cardiomyocytes. However, the addition of adenine (endothelial cells) or adenine with ribose (cardiomyocytes) together with inhibitors of adenosine metabolism protected cells from ATP depletion and further increased adenosine concentration.
...
PMID:Adenine/ribose supply increases adenosine production and protects ATP pool in adenosine kinase-inhibited cardiac cells. 951 42

High energy phosphate levels fall rapidly during cardiac ischemia and recover slowly (more than one week) during reperfusion. The slow recovery of ATP may reflect a lack of purine metabolic precursors and/or increased activity of purine catabolic enzymes such as 5'-nucleotidase (5'-NT, EC 3.1.3.5) and adenosine deaminase (ADA, EC 3.5.4.4). The activity of enzymes involved in both the catabolism of ATP precursors (5-NT and ADA) and the restoration of ATP from slow synthetic pathways [adenosine kinase (AK, EC 2.7.1.20), adenine phosphoribosyl transferase (APRT, EC 2.4.2.7) and hypoxanthine phosphoribosyl transferase (HPRT, EC 2.4.2.8)] may directly affect the rate of ATP recovery. Strategies to enhance recovery will depend on the relative activity of these enzymes following ischemia. Their activity in different species and their response to ischemia are not well characterized. Hence, rapid assay methods for these enzymes would facilitate detailed time course studies of their activities in postischemic myocardium. We modified a single ion-exchange column chromatographic method using DEAE-Sephadex to determine the products of incubation of 5'-NT, AK, APRT and HPRT with their respective substrates. The uniformity of the final product measurement procedure for all assays permits the activities of the four enzymes to be rapidly determined in a single tissue sample and facilitates the study of a large number of samples. This technique should also be useful for enzymes of the pyrimidine metabolic pathway.
...
PMID:Ion-exchange column chromatographic method for assaying purine metabolic pathway enzymes. 961 62

During moderate prolonged myocardial ischemia, the myocardium is dysfuctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow, i.e., a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns to control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". "Short-term hibernating" myocardium can respond to an inotropic stimulation with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. A role for endogenous adenosine in the development of hibernation has been excluded, since neither contractile function, metabolic parameters, nor viability are altered by increased catabolism of endogenous adenosine by infusion of adenosine deaminase. Also activation of ATP-dependent potassium channels is not responsible for "short-term hibernation". "Short-term hibernating" myocardium has, however, reduced calcium responsiveness.
...
PMID:[Short-term hibernating myocardium: circulation, function and metabolism in sustained regional myocardial ischemia]. 982 61

We developed a model of ischemia and reperfusion (I and R) in human ventricular myocytes (CM). CM injury and metabolics were studied after various interventions: endogenous preconditioning (PC) with anoxia, hypoxia, and anoxic or hypoxic supernatants; endogenous PC with or without SPT or adenosine deaminase; and exogenous adenosine PC before, during, or after I or continuously, with or without SPT. To assess the clinical implications of PC and the possible mediating effects of adenosine, patients undergoing elective coronary bypass surgery (CABG) received either a high or low dose of adenosine. Patients not receiving adenosine served as controls. Adenosine levels, high-energy phosphate levels, the metabolic parameters were evaluated from blood samples and left ventricular biopsy samples. Our cellular model studies indicated that preconditioning conferred protection to human CM via an adenosine-mediated pathway. Adenosine simulated PC without a fall in ATP. Adenosine administered to patients during CABG stimulated myocardial metabolism while preventing the degradation of high energy phosphates. A prospective randomized trial of adenosine administered to high-risk patients for myocardial protection is required.
...
PMID:Optimal myocardial preconditioning in humans. 1041 42

The effect of four variables (adenosine, glutamate dehydrogenase, phosphate buffer, and pH) on the measured catalytic concentration of adenosine deaminase (EC 3.5.4.4) was studied by Response Surface Methodology (RSM). This multivariate methodology offers an empirical approach to the study of enzyme assays and allows to detect the interaction between different variables of the system. Response-surface data showed maximum adenosine deaminase catalytic concentration at pH 7.2, adenosine 20 mmol/l, phosphate buffer 200 mmol/l and glutamate dehydrogenase 850 mu kat/l when pleural fluids were used as samples. Optimum conditions for a material containing purified adenosine deaminase from human erythrocytes differed only slightly from that obtained for the pleural fluid.
...
PMID:Optimization of adenosine deaminase assay by response surface methodology. 1066 Aug 5


<< Previous 1 2 3 4 5 6 7 8 9 10

---