Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
19
|
| pubmed:dateCreated |
1997-10-8
|
| pubmed:abstractText |
The four stereoisomers of 1-aminocyclopentane-1,3,4-tricarboxylic acid {ACPT-I (18) and -II (19), (3R, 4R)-III [(-)-20], and (3S,4S)-III [(+)-20]} have been synthesized and evaluated for their effects at glutamate receptors subtypes. ACPTs are ACPD analogues in which a third carboxylic group has been added at position 4 in the cyclopentane ring. None of the ACPT isomers showed a significant effect on ionotropic NMDA, KA, and AMPA receptors. On the other hand, ACPT-II (19) was found to be a general competitive antagonist for metabotropic receptors (mGluRs) and exhibited a similar affinity for mGluR1a (KB = 115 +/- 2 microM), mGluR2 (KB = 88 +/- 21 microM), and mGluR4a (KB = 77 +/- 9 microM), the representative members of group I, II and III mGluRs, respectively. Two other isomers, ACPT-I (18) and (+)-(3S,4S)-ACPT-III [(+)-20], were potent agonists at the group III receptor mGluR4a (EC50 = 7.2 +/- 2.3 and 8.8 +/- 3.2 microM) and competitive antagonists with low affinity for mGluR1a and mGluR2 (KB > 300 microM). Finally, (-)-(3R,4R)-ACPT-III [(-)-20] was a competitive antagonist with poor but significant affinity for mGluR4a (KB = 220 microM). These results demonstrate that the addition of a third carboxylic group to ACPD can change its activity (from agonist to antagonist) and either increase or decrease its selectivity and/or affinity for the various mGluR subtypes.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclopentanes,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tricarboxylic Acids
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
12
|
| pubmed:volume |
40
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3119-29
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9301676-Animals,
pubmed-meshheading:9301676-Binding, Competitive,
pubmed-meshheading:9301676-Cell Line,
pubmed-meshheading:9301676-Cells, Cultured,
pubmed-meshheading:9301676-Cerebellum,
pubmed-meshheading:9301676-Cyclopentanes,
pubmed-meshheading:9301676-GABA Agonists,
pubmed-meshheading:9301676-GABA Antagonists,
pubmed-meshheading:9301676-Humans,
pubmed-meshheading:9301676-Indicators and Reagents,
pubmed-meshheading:9301676-Inositol,
pubmed-meshheading:9301676-Inositol Phosphates,
pubmed-meshheading:9301676-Kinetics,
pubmed-meshheading:9301676-Mice,
pubmed-meshheading:9301676-Molecular Conformation,
pubmed-meshheading:9301676-Molecular Structure,
pubmed-meshheading:9301676-Neurons,
pubmed-meshheading:9301676-Receptors, Metabotropic Glutamate,
pubmed-meshheading:9301676-Recombinant Proteins,
pubmed-meshheading:9301676-Stereoisomerism,
pubmed-meshheading:9301676-Structure-Activity Relationship,
pubmed-meshheading:9301676-Transfection,
pubmed-meshheading:9301676-Tricarboxylic Acids
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes.
|
| pubmed:affiliation |
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes-Paris V, France.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|