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 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 α 1 β 2 γ 2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S)-reticuline behaved as positive allosteric modulator at the α 3, α 5, and α 6 isoforms of GABAA receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S)-reticuline at the α 3 β 2 γ 2 and α 5 β 2 γ 2 GABAA receptors. Interestingly, α 1, α 3, and α 5 were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine-suspected (S)-reticuline metabolites in the rodent brain.
Michelin Recherche et Technique S.A., Route André-Piller 30, 1762 Givisiez, Switzerland.
Milan
M
Fedurco
Department of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
Jana
J
Gregorová
Department of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
Kristýna
K
Šebrlová
Department of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
Jana
J
Kantorová
Department of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
Ondřej
O
Peš
Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
Roland
R
Baur
Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
Erwin
E
Sigel
Department of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
Eva
E
Táborská