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Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D(2) and D(3) Receptors
Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na(+)). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D(2)...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933336/ https://www.ncbi.nlm.nih.gov/pubmed/27379794 http://dx.doi.org/10.1371/journal.pone.0158808 |
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author | Newton, Claire L. Wood, Martyn D. Strange, Philip G. |
author_facet | Newton, Claire L. Wood, Martyn D. Strange, Philip G. |
author_sort | Newton, Claire L. |
collection | PubMed |
description | Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na(+)). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D(2) and dopamine D(3) receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo. |
format | Online Article Text |
id | pubmed-4933336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49333362016-07-18 Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D(2) and D(3) Receptors Newton, Claire L. Wood, Martyn D. Strange, Philip G. PLoS One Research Article Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na(+)). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D(2) and dopamine D(3) receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo. Public Library of Science 2016-07-05 /pmc/articles/PMC4933336/ /pubmed/27379794 http://dx.doi.org/10.1371/journal.pone.0158808 Text en © 2016 Newton et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Newton, Claire L. Wood, Martyn D. Strange, Philip G. Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D(2) and D(3) Receptors |
title | Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D(2) and D(3) Receptors |
title_full | Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D(2) and D(3) Receptors |
title_fullStr | Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D(2) and D(3) Receptors |
title_full_unstemmed | Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D(2) and D(3) Receptors |
title_short | Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D(2) and D(3) Receptors |
title_sort | examining the effects of sodium ions on the binding of antagonists to dopamine d(2) and d(3) receptors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933336/ https://www.ncbi.nlm.nih.gov/pubmed/27379794 http://dx.doi.org/10.1371/journal.pone.0158808 |
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