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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anaerobic protozoon Tritrichomonas foetus was found incapable of de novo purine synthesis by its failure to incorporate radiolabeled glycine or formate into the nucleotide pool. It had, on the other hand, high activities in incorporating adenine, hypoxanthine or inosine. Radiolabel pulse-chase experiments indicated that adenine, hypoxanthine and inosine all entered the pool through conversion to IMP. The parasite contained hypoxanthine phosphoribosyl transferase, adenine deaminase and inosine phosphorylase, but no adenine phosphoribosyl transferase, inosine kinase or inosine phosphotransferase activity. Adenine and inosine had to be converted to hypoxanthine before incorporation. Adenosine was also rapidly converted to hypoxanthine in T. foetus cell-free extracts, but the presence of adenosine kinase in the parasite allowed some conversion of adenosine directly to AMP. Guanine and xanthine were directly incorporated into GMP and XMP, probably due to the guanine and xanthine phosphoribosyl transferase. There were also strong enzyme activities which convert guanosine to guanine and guanine to xanthine. A guanosine phosphotransferase was found in the 10(5) X g sedimentable fraction of T. foetus, and was capable of converting some guanosine to GMP. This network of T. foetus purine salvage suggests the importance of hypoxanthine-guanine-xanthine phosphoribosyl transferase activities in the parasite.
Mol Biochem Parasitol 1983 Aug
PMID:Purine salvage by Tritrichomonas foetus. 663 66

Adenosine dialdehyde (2'-O-[(R)-formyl( adenin -9-yl)methyl]-(R) -glyceraldehyde), which is formed by periodate oxidation of adenosine, was shown to be a potent inhibitor of S- adenosylhomocysteine hydrolase (AdoHcy hydrolase; EC 3.3.1.1) in mouse L929 cells. The inhibitory effects of adenosine dialdehyde on AdoHcy hydrolase were time-dependent, having a rapid onset with complete inhibition occurring within a 15-min incubation period. When mouse L929 cells were preincubated with adenosine dialdehyde for 15 min, then transferred to fresh medium, the AdoHcy hydrolase activity returned to control values within 16 hr. When cycloheximide, an inhibitor of protein synthesis, was included in the incubation medium, recovery of AdoHcy hydrolase activity was not prevented, suggesting that the recovery of enzyme activity was probably due to slow reversal of the inhibitor-enzyme complex. The inhibition of AdoHcy hydrolase by adenosine dialdehyde resulted in a time-dependent increase in endogenous AdoHcy levels. After an initial 15-min lag time, the concentration of AdoHcy continued to increase, reaching a maximum of 1200 pmoles/mg of protein in 12 hr. A slight increase in AdoMet levels was observed. Incubation of mouse L929 cells with adenosine dialdehyde also caused an inhibition of lipid methylation and protein carboxylmethylation which resulted from the compound's effect on AdoHcy hydrolase and the subsequent buildup of endogenous AdoHcy levels. Under the conditions that produce inhibition of AdoHcy hydrolase and AdoMet-dependent methyltransferases, adenosine dialdehyde had no effect on RNA or DNA synthesis. Therefore, adenosine dialdehyde appears to be a useful chemical probe with which to study the physiological role of AdoMet-dependent methylations.
Mol Pharmacol 1984 May
PMID:Effects of adenosine dialdehyde on S-adenosylhomocysteine hydrolase and S-adenosylmethionine-dependent transmethylations in mouse L929 cells. 672 64

Volume overload congestive heart failure in dogs is associated with a reduced myocardial inotropic responsiveness to the exogenous administration of beta-adrenergic agonists [10, 11]. This same blunted inotropic responsiveness to beta-agonists has now been identified in the failing human myocardium [2]. Volume overload congestive heart failure in dogs is also associated with a reduced resting coronary vascular resistance [7, 12] suggesting the possibility of increased myocardial production of a metabolic vasodilator in the failing heart. Adenosine is a metabolic coronary vasodilator [1] and also has recently been shown to antagonize the inotropic action of beta-adrenergic agonists through a mechanism involving action on the sarcolemmal adenylate cyclase system [4, 13]. Given the findings of blunted inotropic responsiveness of the failing myocardium to beta-adrenergic agonists and reduced coronary vascular resistance in heart failure, we hypothesized that heart failure was associated with elevated myocardial production of adenosine. Accordingly we measured myocardial adenosine release in normal dogs and dogs with volume overload heart failure. Basal levels of myocardial adenosine release were found to be elevated three-fold above normal in dogs with heart failure. It is possible that elevated adenosine release in the failing myocardium contributes both to abnormalities of coronary blood flow and to the blunted inotropic responsiveness of the failing heart to catecholamines.
J Mol Cell Cardiol 1984 Jun
PMID:Increased myocardial adenosine release in heart failure. 674 93

Insulin action and insulin binding in isolated rat fat cells incubated with adenosine or adenosine deaminase were studied. Adenosine enhanced the effects of insulin on glucose transport and glucose metabolism. The nucleoside shifted the concentration-response curves of insulin-stimulated D-[3-3H]glucose incorporation into total lipids, and of D-[U-14C]glucose conversion to fatty acids to smaller insulin concentrations. In addition, the maximal response of the fatty acid synthesis was increased. Insulin sensitivity and maximal response to insulin of the glucose transport system, as assessed by the rate of uptake of 2-deoxyglucose and 3-O-methylglucose, were increased by adenosine. The adenosine derivative N6-phenylisopropyladenosine similarly enhanced deoxyglucose transport in the presence of insulin. However, insulin binding was not affected by adenosine. The results suggest that adenosine modulates insulin action at a step distal from the insulin receptor, and before, or at, the glucose transport system.
Mol Pharmacol 1982 Nov
PMID:Modulation of insulin sensitivity by adenosine. Effects on glucose transport, lipid synthesis, and insulin receptors of the adipocyte. 675 15

1. Adenosine analogues inhibit calcium-dependent K+-evoked release of [3H]norepinephrine from guinea pig cerebral cortical and hippocampal vesicular preparations. Inhibition requires high concentrations (100 microM) of the adenosine analogues and is abolished in the presence of high concentrations (2 mM) of calcium ions. The inhibitory effect of 2-chloroadenosine is blocked by theophylline. The structure activity profile (N6-D-phenylisopropyladenosine greater than or equal to N6-L-phenylisopropyladenosine greater than or equal to 2-chloroadenosine greater than N6-cyclohexyladenosine, adenosine 5'-cyclopropylcarboxamide) is not that expected of either A1 (high-affinity) or A2 (low-affinity) adenosine receptors. 2. Calcium-dependent K+-evoked release of [3H]dopamine from guinea pig striatal vesicular preparations is inhibited by apomorphine. However, only 2-chloroadenosine causes an inhibition of K+-evoked release of [3H]dopamine. Other adenosine analogues such as D- and L-phenylisopropyladenosine and adenosine 5'-cyclopropylcarboxamide cause a facilitation of K+-evoked release. The facilitation is abolished or reduced in the presence of high concentrations (2 mM) of calcium ions. The sites of action of adenosine analogues do not appear to have structural requirements identical to those expected of A1 (high-affinity) or A2 (low-affinity) adenosine receptors. 3. The results indicate that adenosine analogues can have either inhibitory or facilitory effects on K+-evoked release of catecholamines from central synaptic terminals.
Cell Mol Neurobiol 1982 Sep
PMID:Release of norepinephrine and dopamine from brain vesicular preparations: effects of adenosine analogues. 715 1

The pathways of purine ribonucleotide synthesis and interconversion that are operative in the intact adult pig lung worm Metastrongylus apri were identified by radioisotope tracing. The rate of [14C]glycine incorporation into purines was low but sufficient to demonstrate synthesis de novo. Radioactively labelled adenine, hypoxanthine and guanine were readily taken up and converted to the corresponding mononucleotides. Most of the AMP and GMP formed were phosphorylated to the triphosphates. These two nucleotides were interconvertable by pathways in which IMP is an intermediate. Adenosine was converted to nucleotides by direct phosphorylation as well as via formation of hypoxanthine. The rate of synthesis of adenine nucleotides from hypoxanthine was 5-7 times that of guanine nucleotides; conversion of IMP to AMP and to xanthosine 5'-monophosphate were the rate-limiting steps.
Mol Biochem Parasitol 1981 Apr
PMID:Pathways of purine ribonucleotide biosynthesis in the adult worm Metastrongylus apri (Nematoda: Metastrongyloidea) from pig lung. 724 68

We investigated the influence of Mg2+ and Mn2+ on the effects of adenosine and some derivatives on basal adenylate cyclase activity in rat fat cell membranes as well as on enzyme activity stimulated by isoprenaline or sodium fluoride. Adenosine and derivatives modified in the ribose function were inhibitory, irrespective of the stimulant used, both in the presence of MgCl2 or MnCl2. Inhibition of basal and sodium fluoride stimulated adenylate cyclase activity was more pronounced in the presence of MnCl2 than in the presence of MgCl2. N6-substituted adenosine analogs proved to be inhibitory in the presence of 5 mM MgCl2, but in the presence of 1 mM MnCl2 the fluoride stimulated adenylate cyclase activity was potentiated, while basal and isoprenaline stimulated activity were not significantly inhibited. These effects of adenosine and derivatives could not be blocked by theophylline with or without guanyl nucleotides. The potentiating effect of N6-substituted adenosine derivatives on sodium fluoride activated adenylate cyclase is dependent on the structure of the N6-substituent and consists of an enhancement of Vmax in combination with a small decrease of the Km for MnATP2-, indicative of an allosteric effect on adenylate cyclase. No potentiation by N6-phenylisopropyladenosine of sodium fluoride stimulated cyclase was found on digitonin solubilized cyclase, while the inhibitory effect of adenosine was retained. The relevance of these findings is discussed in connection with the current hypothesis concerning the presence of two adenosine-sensitive sites on rat fat cell membranes.
Mol Cell Biochem 1981 Oct 30
PMID:Effects of adenosine and adenosine-analogs on adenylate cyclase activity in the rat adipocyte plasma membrane: comparison of the properties of the enzyme with Mn2+ and Mg2+ as divalent cations. 731 71

System for studying DNA synthesis in the isolated nuclei of loach Misgurnus fossilis embryo was described. Nuclei from 13--15 h embryo incorporated 2--3 pmoles of [3H]TMP or [3H]dCMP per microgram of DNA during 30 min of incubation in the reaction mixture. The incorporation was inhibited by ethidium bromide, actinomycin D, and N-ethylmaleimide. The incorporation was Mg2+- and ATP-dependent. Adenosine diphosphate at a concentration of 10 mM enhanced the label incorporation into DNA about twofold. Nicotinamide adenine dinucleotide, polyamines, heparin, and histones inhibited label incorporation into nuclear DNA.
Mol Biol (Mosk)
PMID:[DNA synthesis in isolated nuclei of Misgurnus fossilis loach embryos. I. Characteristics of the system]. 742 21

Three fractions of nascent DNA labeled with [3H]dCTP in isolated nuclei of Misgurnus fossilis embryos were observed after sedimentation in alkaline sucrose: 1) high-molecular-weight DNA strands larger than 3000 nucleotides; 2) fragments of DNA with average length about 200 nucleotides; 3) low-molecular-weight DNA fragments shorter than 100 nucleotides. The labeled DNA was accumulated in the high-molecular-weight fraction (1) with an increase of incubation time. This process indicated the sealing of Okazaki fragments to parental DNA in the course of DNA replication. Adenosine diphosphate stimulated the label accumulation in larger DNA fragments. Embryo nuclei contain Ca-dependent desoxyribonuclease which can digest both exogenous and endogenous DNA DNase I treatment of nuclei dramatically stimulated the label incorporation into nuclear DNA.
Mol Biol (Mosk)
PMID:[DNA synthesis in isolated nuclei of Misgurnus fossilis loach embryos. II. Sedimentation of newly-formed DNA in an alkaline sucrose concentration gradient. Effect of calcium ions]. 744 70

Four native and cloned adenosine receptors (ARs), designated A1AR, A2aAR, A2bAR, and A3AR, have been characterized functionally and by radioligand binding. In the present study, we have used selective antibodies to identify the G protein subunits and phospholipase C (PLC)-beta isoform coupled to A1ARs in smooth muscle membranes and permeabilized muscle cells from rabbit intestine. Immunoblot analysis disclosed the presence of a full complement of G proteins. Adenosine caused contraction of dispersed muscle cells and increases in D-myo-inositol-1,4,5-trisphosphate, intracellular calcium, and cAMP levels. Contraction and the increases in D-myo-inositol-1,4,5-trisphosphate and intracellular calcium levels were abolished by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine and augmented by the A2 antagonist CGS-15943; the reverse occurred with cAMP. A selective A1AR agonist, cyclopentyladenosine, inhibited forskolin-stimulated cAMP accumulation; the inhibition was reversed by treatment of the cells with pertussis toxin or a G alpha i3-specific antibody. The pattern of inhibition implied coexistence of A1ARs and A2ARs coupled to interactive signaling pathways, with A2ARs mediating activation of adenylyl cyclase and A1ARs mediating activation of PLC and inhibition of adenylyl cyclase. Adenosine-stimulated PLC activity in muscle membranes was selectively blocked by G alpha i3- and G beta-specific antibodies, as well as by a PLC-beta 3-specific antibody, but not by antibodies to other PLC-beta isoforms or G proteins. A combination of maximally effective concentrations of G alpha i3- and G beta-specific antibodies did not elicit greater inhibition than did either alone. In contrast, cholecystokinin-stimulated PLC activity was selectively blocked by PLC-beta 1- and G alpha q/11-specific antibodies. Adenosine-stimulated contraction and 45Ca2+ efflux in permeabilized muscle cells were also selectively blocked by G alpha i3-, G beta-, and PLC-beta 3-specific antibodies, whereas cholecystokinin-stimulated contraction was selectively blocked by PLC-beta 1- and G alpha q/11-specific antibodies. The results indicate that A1ARs are coupled to PLC-beta 3 via both alpha and beta gamma subunits of Gi3.
Mol Pharmacol 1995 Jun
PMID:Adenosine A1 receptor-mediated activation of phospholipase C-beta 3 in intestinal muscle: dual requirement for alpha and beta gamma subunits of Gi3. 760 57


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