The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Chronic benzodiazepine agonist treatment produces functional uncoupling of the gamma-aminobutyric acid-benzodiazepine receptor ionophore complex in cortical neurons.

We have investigated the effect of chronic flurazepam HCl treatment on the gamma-aminobutyric acid (GABA)A receptor complex in cultured mammalian cortical neurons. Chronic flurazepam (1-5 microM, for 1-10 days) treatment did not produce any changes in the morphological appearance or the cell protein content of cortical neurons. The basal binding of [3H]flunitrazepam, [3H] Ro15-1788, and [3H]Ro15-4513 was also not altered after the chronic treatment. However, chronic flurazepam treatment produced uncoupling between GABA and pentobarbital sites and the [3H]flunitrazepam binding site. The EC50 values of GABA and pentobarbital were not significantly altered after chronic flurazepam treatment; however, their Emax values were decreased by approximately 50%. The effect of chronic flurazepam treatment on the observed uncoupling was both time and concentration dependent. Furthermore, the binding of [3H]GABA and t-butylbicyclophosphoro[35S]thionate was also not altered by chronic flurazepam treatment. The effect of GABA on 36Cl influx was not altered after chronic flurazepam treatment; however, treatment significantly attenuated the ability of diazepam to enhance GABA-induced 36Cl influx. Chronic flurazepam-induced uncoupling and decreased diazepam efficacy were reversed by the concomitant presence of the benzodiazepine antagonist Ro15-1788, suggesting that these events are mediated via the benzodiazepine receptor site. Taken together, these results suggest that chronic benzodiazepine treatment produces uncoupling of GABA and pentobarbital sites from the benzodiazepine site and decreased coupling between the benzodiazepine site and GABA receptor-gated Cl- channels. The uncoupling and decreased efficacy may be due to an alteration in the levels of various alpha subunits and may be responsible for the tolerance associated with chronic benzodiazepine agonist treatment.[1]


WikiGenes - Universities