Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently observed that the free radical-generating mixture of xanthine and xanthine oxidase (X/XO) can suppress the inhibitory effects of adenosine on synaptic transmission in the hippocampus, but that this action can be mimicked by xanthine alone. We have now clarified the mechanism of these interactions by using the new, potent and highly selective inhibitor of xanthine oxidase, 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (Y-700). Field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region of rat hippocampal slices. X/XO induced a long-lasting increase of fEPSP slope and significantly reduced the presynaptic inhibitory effect of adenosine. Both these actions were prevented by Y-700 at a concentration of only 200nM. Similarly the superfusion of xanthine alone increased fEPSP slope and reduced sensitivity to adenosine but these effects were also prevented by Y-700. The results indicate that the antagonism of adenosine responses by X/XO or by xanthine alone are entirely attributable to the activity of the added or endogenous XO activity, probably generating free radicals, and are not likely to be caused by a direct antagonistic action at the xanthine-sensitive site on the adenosine receptor.
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PMID:The mechanism of inhibition by xanthine of adenosine A1-receptor responses in rat hippocampus. 1524 40

Activation of N-methyl-D-aspartate (NMDA) receptors prevents the neuronal responses to adenosine in hippocampal slices. As NMDA receptor activation leads to the generation of nitric oxide (NO) and superoxide, we have examined whether these can modify neuronal responses to adenosine and mediate the actions of NMDA. Field excitatory postsynaptic potentials were recorded in the CA1 region of rat hippocampal slices. Paired-pulse interactions were studied to localize the observed interactions to presynaptic terminals. The NO donors S-nitroso-N-acetylpenicillamine and diethylamine NONOate induced a long-lasting potentiation (NO-induced potentiation) of field excitatory postsynaptic potential slope and significantly prevented the presynaptic inhibitory effect of adenosine or the A1 receptor agonist N6-cyclopentyladenosine selectively with no effect on responses to baclofen. The superoxide-generating system of xanthine/xanthine oxidase also prevented presynaptic responses to adenosine and this effect was prevented by superoxide dismutase (SOD). The guanylate cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3a]quinoxalin-1-one (10 microM) prevented NO-induced potentiation and the inhibitory effects of S-nitroso-N-acetylpenicillamine and xanthine/xanthine oxidase on adenosine responses. The inhibitory effect of NMDA on adenosine responses was unchanged by 1H-[1,2,4]-oxadiazolo[4,3a]quinoxalin-1-one, indicating that guanosine-3',5-cyclic monophosphate does not mediate this interaction, although it was partially reduced by SOD, suggesting that superoxide might contribute. The reduction of adenosine responses by electrically-induced long-term potentiation was prevented by NO synthase inhibition or SOD. The results indicate that the presynaptic effects of adenosine at presynaptic sites can be prevented by NO or superoxide but that neither of these individually can fully account for the prevention of adenosine responses by NMDA.
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PMID:Blockade of presynaptic adenosine A1 receptor responses by nitric oxide and superoxide in rat hippocampus. 1525 82

The contribution of the NMDA receptors (NMDARs) to synaptic plasticity declines during aging, and the decline is thought to contribute to memory deficits. Here, we demonstrate that an age-related shift in intracellular redox state contributes to the decline in NMDAR responses through Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). The oxidizing agent xanthine/xanthine oxidase (X/XO) decreased the NMDAR-mediated synaptic responses at hippocampal CA3-CA1 synapses in slices from young (3-8 months) but not aged (20-25 months) rats. Conversely, the reducing agent dithiothreitol (DTT) selectively enhanced NMDAR response to a greater extent in aged hippocampal slices. The enhancement of NMDAR responses facilitated induction of long-term potentiation in aged but not young animals. The DTT-mediated growth in the NMDAR response was not observed for the AMPA receptor-mediated synaptic responses. A similar increase was observed by intracellular application of the membrane-impermeable reducing agent, L-glutathione (L-GSH), through the intracellular recording pipette, indicating that the increased NMDAR response was dependent on intracellular redox state. DTT enhancement of the NMDAR response was dependent on CaMKII activity and was blocked by the CaMKII inhibitor--myristoylated autocamtide-2-related inhibitory peptide (myr-AIP)--but not by inhibition of the activity of protein phosphatases--PP1 and calcineurin (CaN/PP2B) or protein kinase C. CaMKII activity assays established that DTT increased CaMKII activity in CA1 cytosolic extracts in aged but not in young animals. These findings indicate a link between oxidation of CaMKII during aging, a decline in NMDAR responses, and altered synaptic plasticity.
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PMID:Intracellular redox state alters NMDA receptor response during aging through Ca2+/calmodulin-dependent protein kinase II. 2013 Feb

Neural circuitry is a self-organizing arithmetic device that converts input to output and thereby remodels its computational algorithm to produce more desired output; however, experimental evidence regarding the mechanism by which information is modified and stored while propagating across polysynaptic networks is sparse. We used functional multineuron calcium imaging to monitor the spike outputs from thousands of CA1 neurons in response to the stimulation of two independent sites of the dentate gyrus in rat hippocampal networks ex vivo. Only pyramidal cells were analyzed based on post hoc immunostaining. Some CA1 pyramidal cells were observed to fire action potentials only when both sites were simultaneously stimulated (AND-like neurons), whereas other neurons fired in response to either site of stimulation but not to concurrent stimulation (XOR-like neurons). Both types of neurons were interlaced in the same network and altered their logical operation depending on the timing of paired stimulation. Repetitive paired stimulation for brief periods induced a persistent reorganization of AND and XOR operators, suggesting a flexibility in parallel distributed processing. We simulated these network functions in silico and found that synaptic modification of the CA3 recurrent excitation is pivotal to the shaping of logic plasticity. This work provides new insights into how microscopic synaptic properties are associated with the mesoscopic dynamics of complex microcircuits.
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PMID:Hippocampal polysynaptic computation. 2191

In the present study, coumarin-bearing three pyridinium and three tetra-alkyl ammonium salts were synthesized. The compounds were fully characterized by 1 H- and 13 C-NMR, LC/MS and IR spectroscopic methods and elemental analyses. The cytotoxic properties of all compounds were tested against human liver cancer (HepG2), human colorectal cancer (Caco-2) and non-cancer mouse fibroblast (L-929) cell lines. Some compounds performed comparable cytotoxicity with standard drug cisplatin. Antibacterial properties of the compounds were tested against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis bacteria, but the compounds did not have any antibacterial effect against both bacteria. Enzyme inhibitory properties of all compounds were tested on the activities of human carbonic anhydrase I and II, and xanthine oxidase. All compounds inhibited both enzymes more effectively than standard drugs, acetazolamide and allopurinol, respectively. The biological evaluation results showed that ionic and water soluble coumarin derivatives are promising structures for further investigations especially on enzyme inhibition field.
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PMID:Water Soluble Coumarin Quaternary Ammonium Chlorides: Synthesis and Biological Evaluation. 3263 71


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