| pubmed-article:2314388 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:2314388 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:2314388 | lifeskim:mentions | umls-concept:C0205145 | lld:lifeskim |
| pubmed-article:2314388 | lifeskim:mentions | umls-concept:C0205681 | lld:lifeskim |
| pubmed-article:2314388 | lifeskim:mentions | umls-concept:C1167622 | lld:lifeskim |
| pubmed-article:2314388 | lifeskim:mentions | umls-concept:C1880022 | lld:lifeskim |
| pubmed-article:2314388 | lifeskim:mentions | umls-concept:C0084397 | lld:lifeskim |
| pubmed-article:2314388 | lifeskim:mentions | umls-concept:C0599682 | lld:lifeskim |
| pubmed-article:2314388 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:2314388 | pubmed:dateCreated | 1990-4-26 | lld:pubmed |
| pubmed-article:2314388 | pubmed:abstractText | The novel reversible and selective inhibitor of monoamine oxidase-A (MAO-A) Ro 41-1049 [N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide HCl] shows inhibition characteristics similar to those of the structurally related reversible MAO-B inhibitors Ro 16-6491 and Ro 19-6327. In the present study, tritiated Ro 41-1049 was used as a high affinity ligand to study the binding characteristics of this inhibitor to MAO-A and its interactions with the enzyme. An homogeneous population of high affinity binding sites for [3H]Ro 41-1049 was found in membrane preparations from human frontal cortex and placenta (Kd = 16.5 +/- 1.4 and 64.4 +/- 19.2 nM, respectively). In frontal cortex the Bmax value for [3H]Ro 41-1049 (2.6 +/- 0.4 pmol/mg of protein) was about one third of the Bmax calculated for the MAO-B-selective ligand [3H]Ro 16-6491. The density of [3H]Ro 41-1049 binding sites in human placenta varied greatly in the different tissue samples investigated, showing an average Bmax of 101.7 +/- 36.5 pmol/mg of protein. Apparent binding equilibrium was reached after 1 hr of incubation at 37 degrees. At this temperature the binding was reversible, with a dissociation t 1/2 of about 35 min. At lower temperatures the radioactivity dissociation was much slower. Among the various drugs tested, only inhibitors of MAO-A were able to effectively prevent [3H]Ro 41-1049 specific binding. As previously reported for the MAO-B ligands [3H]Ro 16-6491 and [3H]Ro 19-6327, the analysis of the membrane-bound radioactivity showed that [3H]Ro 41-1049 was entirely recovered in the form of its aldehyde derivative, indicating that Ro 41-1049 was deaminated by MAO-A. The existence of a Ro 41-1049 adduct reversibly bound to the enzyme active site might explain the inhibition mechanism of this compound. The exposure of the radioligand-enzyme complex to NaBH3CN at pH 4.5 caused the irreversible covalent incorporation of about 70% of the specifically bound radioactivity into a 60-kDa polypeptide. This incorporation was dependent on the pH and on the amount of NaBH3CN added. The presence of MAO-A- but not MAO-B-selective inhibitors prevented the covalent incorporation of [3H]Ro 41-1049. The present results indicate that [3H]Ro 41-1049 is incorporated into a subunit of MAO-A, in the presence of NaBH3CN, and modifies a protein domain that is essential for the enzyme activity.(ABSTRACT TRUNCATED AT 400 WORDS) | lld:pubmed |
| pubmed-article:2314388 | pubmed:language | eng | lld:pubmed |
| pubmed-article:2314388 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2314388 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:2314388 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2314388 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2314388 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2314388 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2314388 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2314388 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:2314388 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:2314388 | pubmed:issn | 0026-895X | lld:pubmed |
| pubmed-article:2314388 | pubmed:author | pubmed-author:Da PradaMM | lld:pubmed |
| pubmed-article:2314388 | pubmed:author | pubmed-author:GalvaM DMD | lld:pubmed |
| pubmed-article:2314388 | pubmed:author | pubmed-author:ImhofRR | lld:pubmed |
| pubmed-article:2314388 | pubmed:author | pubmed-author:CesuraA MAM | lld:pubmed |
| pubmed-article:2314388 | pubmed:author | pubmed-author:BösMM | lld:pubmed |
| pubmed-article:2314388 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:2314388 | pubmed:volume | 37 | lld:pubmed |
| pubmed-article:2314388 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:2314388 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:2314388 | pubmed:pagination | 358-66 | lld:pubmed |
| pubmed-article:2314388 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:2314388 | pubmed:meshHeading | pubmed-meshheading:2314388-... | lld:pubmed |
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| pubmed-article:2314388 | pubmed:meshHeading | pubmed-meshheading:2314388-... | lld:pubmed |
| pubmed-article:2314388 | pubmed:meshHeading | pubmed-meshheading:2314388-... | lld:pubmed |
| pubmed-article:2314388 | pubmed:meshHeading | pubmed-meshheading:2314388-... | lld:pubmed |
| pubmed-article:2314388 | pubmed:meshHeading | pubmed-meshheading:2314388-... | lld:pubmed |
| pubmed-article:2314388 | pubmed:year | 1990 | lld:pubmed |
| pubmed-article:2314388 | pubmed:articleTitle | Characterization of the binding of [3H]Ro 41-1049 to the active site of human monoamine oxidase-A. | lld:pubmed |
| pubmed-article:2314388 | pubmed:affiliation | Department of Pharmacology, University of Milan, Italy. | lld:pubmed |
| pubmed-article:2314388 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:2314388 | pubmed:publicationType | In Vitro | lld:pubmed |
| pubmed-article:2314388 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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