Modulatory Effects ofEschscholzia californicaAlkaloids on Recombinant GABAAReceptors

Abstract

The California poppy (Eschscholzia californicaCham.) 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 inE. californicacould be hypothesized to act at GABAAreceptors, which are widely expressed in the brain mainly at the inhibitory interneurons. Electrophysiological studies on a recombinantα1β2γ2GABAAreceptor showed no effect ofN-methyllaurotetanine at concentrations lower than 30 μM. However, (S)-reticuline behaved as positive allosteric modulator at theα3,α5, andα6isoforms of GABAAreceptors. The depressant properties of aerial parts ofE. californicaare assigned to chloride-current modulation by (S)-reticuline at theα3β2γ2andα5β2γ2GABAAreceptors. Interestingly,α1,α3, andα5were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine—suspected (S)-reticuline metabolites in the rodent brain.