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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1999-5-3
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pubmed:abstractText |
1. We have investigated the antagonist properties of 6 alpha-substituted phenylglycine analogues based on the structure of 4-carboxyphenylglycine (4-CPG) for group I metabotropic glutamate receptors (mGlu1alpha and mGlu5a) permanently expressed in CHO cells. 2. (S)-4-CPG and (S)-MCPG were the most selective mGlu1alpha receptor antagonists. Longer chain alpha-carbon substitutions resulted in a progressive loss of antagonist affinity at mGlu1alpha receptors but not at mGlu5a receptors. Thus mGlu1alpha receptor antagonists require small aliphatic groups at the alpha-position. Alpha-cyclopropyl-4-CPG showed a tendency towards mGlu5a selectivity, suggesting that bulky groups at this position may favour mGlu5a receptor antagonism. 3. We demonstrate that the mGlu5a receptor displays agonist-dependent antagonism. L-glutamate-induced Ca2+ release in mGlu5a receptor expressing cells was more susceptible to antagonism by cyclic alpha-carbon derivatives than (S)-3,5-dihydroxyphenylglycine (DHPG)-induced Ca2+ release in the same cell line. 4. The data presented suggests that mGlu1alpha and mGlu5a receptors have different steric and/or conformational requirements for the binding of antagonists and different amino acids which could interact with agonists. 5. These phenylglycine analogues could provide leads for the development of subtype selective antagonists.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-1309649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-1320017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-1362358,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-7813681,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8035201,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8182479,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8223907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8401919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8719814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8730739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8730745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8742030,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-8871210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-9096163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051137-9295216
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-chloro-5-hydroxyphenylglycine,
http://linkedlifedata.com/resource/pubmed/chemical/3,5-dihydroxyphenylglycine,
http://linkedlifedata.com/resource/pubmed/chemical/4-carboxy-3-hydroxyphenylglycine,
http://linkedlifedata.com/resource/pubmed/chemical/4-carboxyphenylglycine,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoates,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylacetates,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/Resorcinols
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
126
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
205-10
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10051137-Animals,
pubmed-meshheading:10051137-Benzoates,
pubmed-meshheading:10051137-Binding, Competitive,
pubmed-meshheading:10051137-CHO Cells,
pubmed-meshheading:10051137-Calcium,
pubmed-meshheading:10051137-Cricetinae,
pubmed-meshheading:10051137-Excitatory Amino Acid Antagonists,
pubmed-meshheading:10051137-Glutamic Acid,
pubmed-meshheading:10051137-Glycine,
pubmed-meshheading:10051137-Phenylacetates,
pubmed-meshheading:10051137-Receptors, Metabotropic Glutamate,
pubmed-meshheading:10051137-Resorcinols
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pubmed:year |
1999
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pubmed:articleTitle |
Antagonist activity of alpha-substituted 4-carboxyphenylglycine analogues at group I metabotropic glutamate receptors expressed in CHO cells.
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pubmed:affiliation |
Department of Anatomy, School of Medical Sciences, University of Bristol, England, UK. a.doherty@bristol.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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