Chelidonium majus L.: components with in vitro affinity for the GABAA receptor. Positive cooperation of alkaloids.
The influence of an ethanolic dry extract of Chelidonii herba on the GABAA receptor has been studied in vitro. In the presence of 90 micrograms/assay a positive cooperation was induced for [3H]muscimol accompanied by an increase of the specific binding (115%) while 160 micrograms/assay exerted a 50% inhibition of the specific binding of the radioligand [3H]muscimol. The quantitative determination of the Chelidonium alkaloids by HPLC together with the evaluation of the radioreceptor assays of the pure alkaloids revealed that the allosteric modulation of the GABAA receptor is mainly due to protopine. The small amounts of allocryptopine and stylopine assumingly support the action of protopine. Protopine, stylopine, and allocryptopine do not influence the specific binding of [3H]flunitrazepam. Thus, the positive cooperative modulation of the GABAA receptor is not based on an interaction of these alkaloids with the benzodiazepine receptor. The specific [3H]muscimol binding was inhibited only by chelerythrine and sanguinarine with IC50 values of 25 microM and 39 MicroM, respectively. The content of chelerythrine and sanguinarine in the ethanolic dry extract of Chelidonii herba is 500 or even 1000 times too low to account for the observed interference with GABAA receptor activity. Thus, the alkaloids are not responsible for the inhibitory action on the GABAA receptor at higher concentrations of the ethanolic dry extract.
Häberlein
H
H
Institut für Pharmazeutische Biologie der Phillips-Universität, Marburg, Germany.
Tschiersch
K P
KP
Boonen
G
G
Hiller
K O
KO
D000470:Alkaloids / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D014316:Tritium
D000470:Alkaloids; D010936:Plant Extracts; D011963:Receptors, GABA-A; D014316:Tritium; D009118:Muscimol