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

Intact Eimeria tenella sporozoites and merozoites did not incorporate radiolabeled formate or glycine into their purine nucleotides suggesting a lack of de novo purine synthesis. However, [U-14C]glucose was incorporated into the cellular purine and pyrimidine nucleotide pools of both forms probably via conversion to radiolabeled ribose-1-phosphate and/or 5'-phosphoribosyl-1-alpha-pyrophosphate and the resulting action of various purine and pyrimidine salvage enzymes. Both forms of the parasite salvaged radiolabeled purine bases and nucleosides in a similar fashion. These purines were incorporated into ribonucleotides and into RNA and DNA. Adenine and inosine were transformed to hypoxanthine. Adenosine was converted to both inosine and hypoxanthine. Hypoxanthine and xanthine were not oxidized to uric acid but were metabolized to nucleotides. Guanosine was cleaved to guanine; guanine was deaminated to xanthine. The results demonstrate the presence of several purine salvage pathways. Purine phosphoribosylating and nucleoside phosphorylating activities as well as purine nucleoside cleaving and adenosine, adenine and guanine deaminating activities were evident. The metabolic evidence suggests the enzymes required to convert the newly formed nucleoside monophosphates to ATP and GTP were present also.
Mol Biochem Parasitol 1985 Jan
PMID:Purine metabolism in the intact sporozoites and merozoites of Eimeria tenella. 258 Feb 36

The A1 adenosine receptor of rat brain membranes has been solubilized with digitonin and purified approximately 150-fold by affinity chromatography. The digitonin-solubilized receptor, which can be labeled with 8-cyclopentyl-1,3-[3H]dipropylxanthine([3H]DPCPX), was adsorbed on xanthine amine congener (XAC)-linked agarose. The interaction of the solubilized receptor activity with the affinity gel was biospecific. Adenosine agents blocked adsorption of solubilized receptor activity to the XAC-agarose with the appropriate A1 adenosine selectivity. For agonists, 8-cyclopentyladenosine greater than (R)-phenylisopropyladenosine greater than CV-1808, whereas, for antagonists, 8-cyclopentyltheophylline (CPT) greater than XAC greater than isobutylmethylxanthine = theophylline. The same A1 adenosine receptor specificity was observed for elution of [3H]DPCPX binding activity from the gel. XAC-agarose adsorbed 65-80% of the solubilized [3H]DPCPX binding activity and, after the gel was washed, 30-40% of the adsorbed activity could be eluted with 100 microM CPT, with specific binding activity of approximately 60 pmol/mg of protein. The order of potency of adenosine agonists [8-cyclopentyladenosine greater than (R)-phenylisopropyladenosine greater than 5'-N-ethylcarboxamidoadenosine greater than (S)-phenylisopropyladenosine] and antagonists (DPCPX greater than XAC greater than CPT greater than isobutylmethylxanthine) with the affinity-purified preparation was found to be similar to that of the solubilized adenosine A1 receptor. This affinity chromatography procedure should prove to be valuable in the isolation and molecular characterization of A1 adenosine receptors.
Mol Pharmacol 1989 Jun
PMID:Affinity chromatography of A1 adenosine receptors of rat brain membranes. 273 95

Effects of adenosine analogues on adenylate cyclase activity in preovulatory rat ovarian membranes were studied. Adenosine analogues stimulated adenylate cyclase activity in the following rank order of potency: NECA (5'-(N-ethyl)carboxamidoadenosine) greater than 2-chloroadenosine greater than N6-(R-phenylisopropyl)-adenosine greater than N6-(S-phenylisopropyl)adenosine. The apparent EC50 for NECA was 0.28 microM. The adenosine receptor antagonist 8-phenyltheophylline (10 microM) displaced the dose-response curve for NECA to the right, increasing the EC50 for NECA about one order of magnitude. NECA also additively increased maximally FSH-stimulated adenylate cyclase activity. These results suggest that adenosine stimulates adenylate cyclase in rat ovarian membranes via adenosine receptors of the A2 type.
Mol Cell Endocrinol 1988 Apr
PMID:Evidence for A2 adenosine receptor-mediated effects on adenylate cyclase activity in rat ovarian membranes. 283 46

The involvement of adenosine in the coupling of insulin binding to action was investigated in rat adipocytes. Reduction of endogenous adenosine levels by treatment with adenosine deaminase (ADA) had no significant effect on either basal or maximally stimulated glucose transport, but reduced the insulin sensitivity of transport stimulation. Adenosine deaminase treatment also shifted the EC50 of H2O2 stimulation of transport from 0.13 mM to 0.30 mM, and the EC50 for insulin stimulation of protein synthesis from 0.40 +/- 0.06 ng/ml to 1.30 +/- 0.25 ng/ml. Adenosine appears to be acting through the pharmacological Ri adenosine receptor subtype. The mode of action of adenosine does not seem to involve inhibition of adenylate cyclase. Adenosine also influences the kinetics of insulin action. ADA treatment slows the onset of transport stimulation by a maximal insulin concentration (10 ng/ml). Increasing the hormone level to 100 ng/ml overcomes this slowing without increasing transport further. The deactivation of glucose transport following removal of insulin is accelerated by ADA treatment. Thus, adenosine is involved both in maintaining a high efficiency of an early step in the insulin signaling process and in maintaining optimal activity of the insulin-stimulated glucose transport system.
Mol Cell Endocrinol 1988 Nov
PMID:The role of adenosine in insulin action coupling in rat adipocytes. 285 Sep 47

The smooth endoplasmic reticulum (ER) and cytosol fractions of liver homogenates exhibit phosphoprotein phosphatase activity towards glycogen synthase D and phosphorylase a. The following observations suggest that liver contains multiple forms of these phosphatases. Synthase phosphatase activity in either fraction was more readily inactivated by heating than phosphorylase phosphatase activity. Both synthase phosphatase and phosphorylase phosphatase activities in smooth ER were non-competitively inhibited by Mg2+, but were activated by this ion in the cytosol. Synthase phosphatase activities in cytosol and smooth ER were stimulated by a number of sugar phosphates, particularly glucose-1-phosphate, galactose-6-phosphate and fructose-6-phosphate. Erythrose-4-phosphate stimulated synthase phosphatase activity in the cytosol, but inhibited the microsomal enzyme. Phosphorylase phosphatase activities in either fraction were inhibited by most sugar phosphates. Adenosine mono-, di- and tri-phosphates inhibited phosphatase activities in both fractions. Low concentrations of AMP and ADP inhibited phosphorylase phosphatase activities to a greater extent than synthase phosphatase activities. Chromatography of the smooth ER fraction on DEAE-cellulose resulted in the separation of synthase phosphatase from phosphorylase phosphatase, as soluble proteins. The elution profile for the microsomal phosphatase was different from that for the cytosol enzymes. It is concluded that: both synthase phosphatase and phosphorylase phosphatase in liver have at least two isoenzyme forms; synthase phosphatase and phosphorylase phosphatase are separate enzymes; the different behaviour of microsomal and cytosol phosphatases towards divalent cations and sugar phosphates provides a potential mechanism for the differential regulation of these activities in liver.
Mol Cell Biochem 1985 Mar
PMID:Multiple forms of synthase D phosphatase and phosphorylase a phosphatase in liver and regulatory effects of metabolites on their activities. 298 42

The adenosine concentration of exudate formed on the surface of isolated perfused rat hearts has been used to obtain estimates of interstitial values. At a constant perfusion of approximately 15 ml/min/g, exudate was collected from below ring seals that either fitted snugly (compressing seals) or that acted as wicks (wicking seals) to deflect venous effluent away from the apical surface. Steady state exudates flows obtained below each of these seals were 0.96 +/- 0.05 ml/min and 0.18 +/- 0.02 ml/min, respectively. Adenosine concentration of surface exudate and venous effluent from hearts with the compressing seal were 130 +/- 8 nM and 23 +/- 3 nM, respectively, and from those with the wicking seal were 770 +/- 93 nM and 36 +/- 9 nM, respectively. Interstitial adenosine concentration in a situation with no net filtration may be slightly higher than that achieved in the exudate from preparations with the wicking seal. Addition of exogenous adenosine to the perfusate (1.0 microM) decreased vascular resistance and automaticity of all preparations, increased the venous effluent adenosine concentration to 236 +/- 18 nM and 251 +/- 30 nM with the compressing and wicking seals, respectively, but did not significantly alter the exudate adenosine concentration with either of the seals. This finding suggests that increases in vascular adenosine may influence functional characteristics without altering interstitial levels. Perfusion with 10 microM adenosine increased adenosine concentration in both effluent and exudate in all preparations but the gradient was reversed so that effluent levels were significantly higher than exudate levels. We conclude that venous adenosine determinations significantly underestimate the interstitial adenosine concentration associated with endogenous adenosine production and significantly overestimate the interstitial levels achieved by infusion of exogenous adenosine.
J Mol Cell Cardiol 1988 Jun
PMID:Estimates of interstitial adenosine from surface exudates of isolated rat hearts. 321 5

An adenosine-sensitive adenylate cyclase has been demonstrated in rat posterior pituitary in the present studies. N-Ethylcarboxamide adenosine (NECA), 2-chloroadenosine (2-Cl-Ado) and L-N6-phenylisopropyladenosine (PIA) all stimulated adenylate cyclase in a concentration-dependent manner, with an apparent Ka between 0.5 and 1 microM. NECA was most effective and stimulated adenylate cyclase by about 100%, whereas 2-Cl-Ado and PIA stimulated the enzyme activity by about 60%. The activation of adenylate cyclase by NECA was dependent on the concentrations of metal ions such as Mg2+ or Mn2+. The stimulatory effect of NECA on adenylate cyclase was completely blocked by 3-isobutyl-1-methylxanthine (IBMX) and 8-phenyltheophylline. Adenosine showed a biphasic effect on adenylate cyclase: stimulation at lower concentrations and inhibition at higher concentrations, whereas 2'-deoxyadenosine and 2'5'-dideoxyadenosine inhibited adenylate cyclase in a concentration-dependent manner. In addition, dopamine, isoproterenol and forskolin also stimulated adenylate cyclase to various degrees and the stimulatory effect of isoproterenol and forskolin was found to be additive with the stimulation exerted by NECA. These data indicate the presence of adenosine stimulatory receptors Ra/A2 in posterior pituitary which are coupled to adenylate cyclase. It is possible that adenosine may act as one of the important regulators to regulate and/or modulate the release of posterior pituitary hormones.
Mol Cell Endocrinol 1988 Jun
PMID:Adenosine interaction with adenylate cyclase in rat posterior pituitary. 340 62

Adenosine dialdehyde (2'-O-[(R)-formyl(adenin-9-yl)methyl]-(R)-glyceraldehyde), formed by periodate oxidation of adenosine, is a potent inhibitor of S-adenosylhomocysteine hydrolase (EC 3.3.1.1.) in mouse L929 cells. Consequently, the dialdehyde produces an increase in intracellular levels of S-adenosylhomocysteine and subsequent inhibition of S-adenosylmethionine-dependent macromolecular methylations. In the present study we show that adenosine dialdehyde is also a potent inhibitor of vaccinia virus plaque formation in monolayer cultures of L cells. When added to the culture medium immediately following attachment of the virus, concentrations of the dialdehyde as low as 0.5 microM produce greater than 90% inhibition of plaque formation after 72 hr. The efficacy of the compound is greatest when added within 8 hr of virus attachment and gradually decreases in a time-dependent manner when added after this point. Treatment of L cells with 5 microM adenosine dialdehyde for 60 min prior to virus infection causes a transient, but virtually complete loss of S-adenosylhomocysteine hydrolase activity and subsequent 3-fold increase in the intracellular S-adenosylhomocysteine/S-adenosylmethionine ratio. Continuous exposure of infected cells to the dialdehyde results in prolonged inhibition of S-adenosylhomocysteine hydrolase accompanied by a 10-fold increase in the S-adenosylhomocysteine/S-adenosylmethionine ratio. Associated with these changes in the dialdehyde-treated, infected cells are an inhibition of early virus-specific protein synthesis and a 13% decrease in methylation of the cytoplasmic poly A+-mRNA. The antiviral action of this compound thus appears to be related to a decrease in viral mRNA methylation (e.g., the 5'-terminal cap structure) which results in suppressed translation of viral proteins essential for virus replication.
Mol Pharmacol 1987 May
PMID:Adenosine dialdehyde: a potent inhibitor of vaccinia virus multiplication in mouse L929 cells. 357 93

The nucleoside analogue, 3-deazaadenosine (c3-Ado), serves both as a substrate and as an inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, and the ability of this compound to induce accumulation of intracellular AdoHcy and S-3-deazaadenosylhomocysteine (c3-AdoHcy) in various cells and species has been widely documented. We here report on the effect of c3-Ado on the disposition of homocysteine (Hcy) and c3-AdoHcy in isolated rat hepatocytes and in non-transformed (Cl 8) and malignant (Cl 16) C3H/10T1/2 mouse embryo fibroblasts in culture. Both the liver cells and fibroblasts release large amounts of Hcy into the extracellular medium, whereas small amounts are retained within the cells. c3-Ado (100-300 microM) nearly completely inhibits cellular Hcy egress. Intracellular Hcy in liver cells exposed to c3-Ado is in fact increased in proportion to intracellular buildup of AdoHcy, whereas c3-Ado nearly deprives the malignant Cl 16 cells of intracellular Hcy and decreases it markedly in Cl 8 cells. Adenosine exerts a similar effect as c3-Ado on Hcy and AdoHcy in liver cells, but concentrations in the mM range are required, and the effect subsides within hours. In liver cells, c3-Ado(300 microm) induces a higher level of c3-AdoHcy than of AdoHcy. In the malignant (Cl 16) fibroblasts, c3-AdoHcy content approaches the amount of AdoHcy whereas, in the non-transformed (Cl 8) fibroblasts, relatively small amounts of c3-AdoHcy are formed. Notably, c3-AdoHcy is released from all cell types in proportion to the intracellular amount, suggesting that c3-AdoHcy is efficiently handled by the mechanism responsible for the cellular egress of nucleosidylhomocysteine. The possible role of Hcy and c3-AdoHcy in the mechanism of action of c3-Ado is discussed.
Mol Pharmacol 1986 Aug
PMID:Disposition of homocysteine and S-3-deazaadenosylhomocysteine in cells exposed to 3-deazaadenosine. 373 40

Regulation of coronary flow as a function of myocardial energy expenditure was investigated in isolated perfused rat hearts electrically paced at the desired frequencies. The sinoatrial node was excised to lower the endogenous heart rate. The main covariants measured were phosphagen, inorganic phosphate, adenosine, inosine and hypoxanthine concentrations in the tissue, washout of nucleosides and hypoxanthine into the perfusate, oxygen consumption and coronary flow. Oxygen consumption was linearly correlated with heart rate and coronary flow, while the correlation between coronary flow and perfusate adenosine was nonlinear. The adenosine concentrations in the tissue and perfusate showed a mirror image curvilinearity reminiscent of a threshold pattern for adenosine washout. The tissue adenosine content had a negative linear correlation with the adenylate phosphorylation potential (long(ATP/ADP X Pi)). Adenosine output was linearly correlated with free AMP concentration in the tissue, the latter being calculated from the equilibrium of the adenylate kinase reaction. The results confirm the correlation between cellular energy state and coronary flow and support the notion that the mediators between the former and the vascular smooth muscle involve the concentration of free AMP in the tissue, suggesting that the formation of adenosine may be limited by the availability of AMP. The results are in agreement with the hypothesis that adenosine is the diffusible extracellular mediator in the energy-linked regulation of coronary flow.
J Mol Cell Cardiol 1986 Nov
PMID:Role of cellular energy state and adenosine in the regulation of coronary flow during variation in contraction frequency in an isolated perfused heart. 379 75


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