Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model
N-methyl-D-aspartic acid receptor (NMDAr) activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5′-phosphate-dependent serine racemase (SR). D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS) and L-erythro-3-hydroxyas...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/2012/279147 |
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| _version_ | 1832561764539039744 |
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| author | Claudio Laurido Alejandro Hernández Teresa Pelissier Luis Constandil |
| author_facet | Claudio Laurido Alejandro Hernández Teresa Pelissier Luis Constandil |
| author_sort | Claudio Laurido |
| collection | DOAJ |
| description | N-methyl-D-aspartic acid receptor (NMDAr) activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5′-phosphate-dependent serine racemase (SR). D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS) and L-erythro-3-hydroxyaspartate (LEHA), among others, have proven to be effective in reducing the D-serine levels in culture cells. It is tempting then to try these compounds in their effectiveness to decrease nociceptive levels in rat arthritic pain. We measured the C-reflex paradigm and wind-up potentiation in the presence of intrathecally injected LSOS (100 μg/10 μL) and LEHA (100 μg/10 μL) in normal and monoarthritic rats. Both compounds decreased the wind-up activity in normal and monoarthritic rats. Accordingly, all the antinociceptive effects were abolished when 300 μg/10 μL of D-serine were injected intrathecally. Since no in vivo results have been presented so far, this constitutes the first evidence that SR inhibitions lower the D-serine levels, thus decreasing the NMDAr activity and the consequent development and maintenance of chronic pain. |
| format | Article |
| id | doaj-art-5092270c8bb84daba95054dba148e160 |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-5092270c8bb84daba95054dba148e1602025-02-03T01:24:17ZengWileyThe Scientific World Journal1537-744X2012-01-01201210.1100/2012/279147279147Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain ModelClaudio Laurido0Alejandro Hernández1Teresa Pelissier2Luis Constandil3Laboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChileLaboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChilePrograma de Farmacología Molecular y Clínica, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileLaboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChileN-methyl-D-aspartic acid receptor (NMDAr) activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5′-phosphate-dependent serine racemase (SR). D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS) and L-erythro-3-hydroxyaspartate (LEHA), among others, have proven to be effective in reducing the D-serine levels in culture cells. It is tempting then to try these compounds in their effectiveness to decrease nociceptive levels in rat arthritic pain. We measured the C-reflex paradigm and wind-up potentiation in the presence of intrathecally injected LSOS (100 μg/10 μL) and LEHA (100 μg/10 μL) in normal and monoarthritic rats. Both compounds decreased the wind-up activity in normal and monoarthritic rats. Accordingly, all the antinociceptive effects were abolished when 300 μg/10 μL of D-serine were injected intrathecally. Since no in vivo results have been presented so far, this constitutes the first evidence that SR inhibitions lower the D-serine levels, thus decreasing the NMDAr activity and the consequent development and maintenance of chronic pain.http://dx.doi.org/10.1100/2012/279147 |
| spellingShingle | Claudio Laurido Alejandro Hernández Teresa Pelissier Luis Constandil Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model The Scientific World Journal |
| title | Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model |
| title_full | Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model |
| title_fullStr | Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model |
| title_full_unstemmed | Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model |
| title_short | Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model |
| title_sort | antinociceptive effect of rat d serine racemase inhibitors l serine o sulfate and l erythro 3 hydroxyaspartate in an arthritic pain model |
| url | http://dx.doi.org/10.1100/2012/279147 |
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