Positive Cooperation of Protoberberine Type 2 Alkaloids from Corydalis cava on the GABA_A Binding Site

 

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Abstract

Protoberberine alkaloids from the rhizomes of Corydalis cava were investigated with regard to their influence on the GABA_A receptor using radioreceptor assays. Whereas the protoberberine type 2 alkaloids, isoapocavidine, corydaline, tetrahydropalmatine, scoulerine and isocorypalmine, increased the specific [³H]BMC-binding in a range of 21 - 49 %, the protoberberine type 1 alkaloids, palmatine, coptisine, dehydroapocavidine, and dehydrocorydaline, had no influence on the binding behaviour of the GABA_A receptor. To confirm the modulatory activity of the protoberberine type 2 alkaloids on living cells, GABA_A receptor binding studies were performed by fluorescence correlation spectroscopy (FCS) using hippocampal neurons and the fluorescently labelled ligand, muscimol-Alexa (Mu-Alexa). The incubation of hippocampal neurons with 7.5 nM Mu-Alexa showed a specific binding of 5.25 nM (70 %). The evaluation of the autocorrelation curve revealed two different mobilities of receptor ligand complexes, D_bound1 = (2.8 ± 0.91) μm²/s for the free lateral mobility and D_bound2 = (0.14 ± 0.05) μm²/s for the hindered mobility. An incubation of hippocampal neurons with 7.5 nM Mu-Alexa and 7.5 nM scoulerine showed a maximal increase of the specific Mu-Alexa binding of approximately 27 % by selectively modulating the amount of receptor-ligand complexes with a hindered mobility (9 % to 27 %).

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Prof. Dr. H. Häberlein

Physiological Chemistry

University of Bonn

Nussallee 11

53115 Bonn

Germany

Email: haeberlein@institut.physiochem.uni-bonn.de

Fax: +49-228-732416