Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors
The California poppy (Eschscholzia californica Cham.) contains a variety of natural compounds including several alkaloids found exclusively in this plant. Because of the sedative, anxiolytic, and analgesic effects, this herb is currently sold in pharmacies in many countries. However, our understandi...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Biochemistry Research International |
| Online Access: | http://dx.doi.org/10.1155/2015/617620 |
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| author | Milan Fedurco Jana Gregorová Kristýna Šebrlová Jana Kantorová Ondřej Peš Roland Baur Erwin Sigel Eva Táborská |
| author_facet | Milan Fedurco Jana Gregorová Kristýna Šebrlová Jana Kantorová Ondřej Peš Roland Baur Erwin Sigel Eva Táborská |
| author_sort | Milan Fedurco |
| collection | DOAJ |
| description | The California poppy (Eschscholzia californica Cham.) contains a variety of natural compounds including several alkaloids found exclusively in this plant. Because of the sedative, anxiolytic, and analgesic effects, this herb is currently sold in pharmacies in many countries. However, our understanding of these biological effects at the molecular level is still lacking. Alkaloids detected in E. californica could be hypothesized to act at GABAA receptors, which are widely expressed in the brain mainly at the inhibitory interneurons. Electrophysiological studies on a recombinant α1β2γ2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S)-reticuline behaved as positive allosteric modulator at the α3, α5, and α6 isoforms of GABAA receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S)-reticuline at the α3β2γ2 and α5β2γ2 GABAA receptors. Interestingly, α1, α3, and α5 were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine—suspected (S)-reticuline metabolites in the rodent brain. |
| format | Article |
| id | doaj-art-09a9f2869ffa48d4a377d39f5d28495f |
| institution | Kabale University |
| issn | 2090-2247 2090-2255 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Biochemistry Research International |
| spelling | doaj-art-09a9f2869ffa48d4a377d39f5d28495f2025-02-03T01:01:02ZengWileyBiochemistry Research International2090-22472090-22552015-01-01201510.1155/2015/617620617620Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA ReceptorsMilan Fedurco0Jana Gregorová1Kristýna Šebrlová2Jana Kantorová3Ondřej Peš4Roland Baur5Erwin Sigel6Eva Táborská7Michelin Recherche et Technique S.A., Route André-Piller 30, 1762 Givisiez, SwitzerlandDepartment of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech RepublicDepartment of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech RepublicDepartment of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech RepublicDepartment of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech RepublicInstitute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, SwitzerlandInstitute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, SwitzerlandDepartment of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech RepublicThe California poppy (Eschscholzia californica Cham.) contains a variety of natural compounds including several alkaloids found exclusively in this plant. Because of the sedative, anxiolytic, and analgesic effects, this herb is currently sold in pharmacies in many countries. However, our understanding of these biological effects at the molecular level is still lacking. Alkaloids detected in E. californica could be hypothesized to act at GABAA receptors, which are widely expressed in the brain mainly at the inhibitory interneurons. Electrophysiological studies on a recombinant α1β2γ2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S)-reticuline behaved as positive allosteric modulator at the α3, α5, and α6 isoforms of GABAA receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S)-reticuline at the α3β2γ2 and α5β2γ2 GABAA receptors. Interestingly, α1, α3, and α5 were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine—suspected (S)-reticuline metabolites in the rodent brain.http://dx.doi.org/10.1155/2015/617620 |
| spellingShingle | Milan Fedurco Jana Gregorová Kristýna Šebrlová Jana Kantorová Ondřej Peš Roland Baur Erwin Sigel Eva Táborská Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors Biochemistry Research International |
| title | Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors |
| title_full | Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors |
| title_fullStr | Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors |
| title_full_unstemmed | Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors |
| title_short | Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors |
| title_sort | modulatory effects of eschscholzia californica alkaloids on recombinant gabaa receptors |
| url | http://dx.doi.org/10.1155/2015/617620 |
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