title: Positive cooperation of protoberberine type 2 alkaloids from Corydalis cava on the GABA(A) binding site.
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 [(3)H]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) microm 2/s for the free lateral mobility and D bound2 = (0.14 +/- 0.05) microm 2/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 %).
authors.affiliation: Department of Pharmaceutical Biology, Philipps-University, Marburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Halbsguth
authors.forename: Oliver
authors.initials: O
authors.lastname: Meissner
authors.forename: Hanns
authors.initials: H
authors.lastname: Häberlein
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D031311:Corydalis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D013050:Spectrometry, Fluorescence
chemical_list: D000470:Alkaloids; D001600:Berberine Alkaloids; D010936:Plant Extracts; D011963:Receptors, GABA-A; C009090:protoberberine