Planta Med 2003; 69(4): 305-309
DOI: 10.1055/s-2003-38869
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

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

Christiane Halbsguth1 , Oliver Meißner1 , Hanns Häberlein2
  • 1Department of Pharmaceutical Biology, Philipps-University, Marburg, Germany
  • 2Physiological Chemistry, University of Bonn, Bonn, Germany
Further Information

Publication History

Received: August 19, 2002

Accepted: October 27, 2002

Publication Date:
23 April 2003 (online)

Abstract

Protoberberine alkaloids from the rhizomes of Corydalis cava were investigated with regard to their influence on the GABAA 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 GABAA receptor. To confirm the modulatory activity of the protoberberine type 2 alkaloids on living cells, GABAA 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, Dbound1 = (2.8 ± 0.91) μm2/s for the free lateral mobility and Dbound2 = (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