Extract matrix composition does not affect in vitro leukotriene inhibitory effects of the Petasites hybridus extract Ze 339.

It has been shown that a lipophilic CO-extract prepared from the leaves of Petasites hybridus (Ze 339) inhibited leukotriene synthesis in vitro and ex vivo. The inhibition of the leukotriene synthesis was solely attributed to the sum of the petasins, namely petasin and its isomers isopetasin and neopetasin. To further investigate the influence of the extract matrix on leukotriene synthesis inhibition, we compared twelve selected batches of Ze 339 that differed significantly in the composition of the extract matrix.

Loss of zolpidem efficacy in the hippocampus of mice with the GABAA receptor gamma2 F77I point mutation.

Zolpidem is a hypnotic benzodiazepine site agonist with some gamma-aminobutyric acid (GABA)(A) receptor subtype selectivity. Here, we have tested the effects of zolpidem on the hippocampus of gamma2 subunit (gamma2F77I) point mutant mice. Analysis of forebrain GABA(A) receptor expression with immunocytochemistry, quantitative [(3)H]muscimol and [(35)S] t-butylbicyclophosphorothionate (TBPS) autoradiography, membrane binding with [(3)H]flunitrazepam and [(3)H]muscimol, and comparison of miniature inhibitory postsynaptic current (mIPSC) parameters did not reveal any differences between homozygous gamma2I77/I77 and gamma2F77/F77 mice.

Abolition of zolpidem sensitivity in mice with a point mutation in the GABAA receptor gamma2 subunit.

Agonists of the allosteric benzodiazepine site of GABAA receptors bind at the interface of the alpha and gamma subunits. Here, we tested the in vivo contribution of the gamma2 subunit to the actions of zolpidem, an alpha1 subunit selective benzodiazepine agonist, by generating mice with a phenylalanine (F) to isoleucine (I) substitution at position 77 in the gamma2 subunit. The gamma2F77I mutation has no major effect on the expression of GABAA receptor subunits in the cerebellum.

Positive cooperation of protoberberine type 2 alkaloids from Corydalis cava on the GABA(A) binding site.

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).