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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The metabotropic glutamate receptors 5 (mGlu5Rs) and the adenosine A2A receptors (A2ARs) have been reported to functionally interact in the striatum. The aim of the present work was to verify the hypothesis that the state of activation of A2A Rs could influence mGlu5R-mediated effects in the striatum. In electrophysiological experiments (extracellular recording in rat corticostriatal slices), the ability of the selective mGlu5R agonist CHPG to potentiate the reduction of the field potential amplitude induced by NMDA was prevented not only by the selective mGlu5R antagonist MPEP, but also by the selective A2AR antagonist ZM 241385. Analogously, the application of CHPG potentiated NMDA-induced toxicity (measured by LDH release) in cultured striatal neurons, an effect that was abolished by both MPEP and ZM 241385. Finally, the A2AR agonist CGS 21680 potentiated CHGP effects, an action that was reproduced and abolished, respectively, by forskolin (an activator of the cAMP/protein kinase A, PKA, pathway) and KT 5720 (a PKA inhibitor). The results indicate that A2ARs exert a permissive role on mGlu5R-induced effects in the striatum. Such an interaction may represent an additional target for the development of therapeutic strategies towards striatal disorders.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Hippocampal metabotropic glutamate 5 receptors (mGlu5Rs) regulate both physiological and pathological responses to glutamate. Because mGlu5R activation enhances NMDA-mediated effects, and given the role played by NMDA receptors in synaptic plasticity and excitotoxicity, modulating mGlu5R may influence both the physiological and the pathological effects elicited by NMDA receptor stimulation. We evaluated whether adenosine A2A receptors (A2ARs) modulated mGlu5R-dependent effects in the hippocampus, as they do in the striatum. Co-application of the A2AR agonist CGS 21680 with the mGlu5R agonist (RS)-2-chloro-s-hydroxyphenylglycine(CHPG) synergistically reduced field excitatory postsynaptic potentials in the CA1 area of rat hippocampal slices. Endogenous tone at A2ARs seemed to be required to enable mGlu5R-mediated effects, as the ability of CHPG to potentiate NMDA effects was antagonized by the selective A2AR antagonist ZM 241385 in rat hippocampal slices and cultured hippocampal neurons, and abolished in the hippocampus of A2AR knockout mice. Evidence for the interaction between A2ARs and mGlu5Rs was further strengthened by demonstrating their co-localization in hippocampal synapses. This is the first evidence showing that hippocampal A2ARs and mGlu5Rs are co-located and act synergistically, and that A2ARs play a permissive role in mGlu5R receptor-mediated potentiation of NMDA effects in the hippocampus.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science
    Alimentary pharmacology & therapeutics 10 (1996), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Sulphasalazine and 5-amino salicyclic acid drugs are specifically indicated for the treatment of inflammatory bowel disease. Aim: To use drug consumption by a given population as a marker to estimate the number of patients with inflammatory bowel disease. Methods: Prescriptions for sulphasalazine and mesalazine were identified for the 133000 inhabitants of a local health unit in Rome. Other prescriptions received by the patients, who were users of sulphasalazine or mesalazine, were also studied. Results: 99465 patients received at least one prescription for any drug in 1991. Three hundred and seventy-six patients were prescribed sulphasalazine and/or mesalazine, an average of 3.8 prescriptions per patient. These patients were exposed more frequently than the general population to other drugs often used in inflammatory bowel disease treatment, for example, corticosteroids, anti-diarrhoeal drugs and intestinal anti-infectives. We identified that 258 of 100000 inhabitants were prescribed either sulphasalazine or mesalazine; 127 of 100000 inhabitants received full-dose treatment for at least 30 days, and 42.8 of 100000 inhabitants received prescriptions of either drug, also associated with systemic corticosteroids. Conclusion: The consumption of drugs used specifically for inflammatory bowel disease may act as a marker for the prevalence of the condition in a community.
    Type of Medium: Electronic Resource
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