Honokiol and magnolol increase the number of [3H] muscimol binding sites three-fold in rat forebrain membranes in vitro using a filtration assay, by allosterically increasing the affinities of low-affinity sites.

摘要: 1. The bark of the root and stem various Magnolia species has been used in Traditional Chinese Medicine to treat a variety disorders including anxiety nervous disturbances. biphenolic compounds honokiol (H) magnolol (M), main components medicinal plant officinalis, interact with GABAA receptors rat brain vitro. We compared effects H M on [3H]muscimol (MUS) [3H]flunitrazepam (FNM) binding using EDTA/water dialyzed membranes buffer containing 150 mM NaCl plus 5 Tris-HCl, pH 7.5 as well [35S]t-butylbicyclophosphorothionate (TBPS) 200 KBr 7.5. had similar enhancing [3H]MUS [3H]FNM membrane preparations, but was 2.5 5.2 times more potent than M. 2. [ 3 H]FNM binding. GABA alone almost doubled EC50 = 450 nM forebrain cerebellar membranes, respectively. In presence μM or values for were decreased 79 89 nM, respectively, forebrain, 39 78 membranes. potently enhanced potentiating effect 0.61 1.6 maximal enhancements 33 47%, Using corresponding 0.25 1.1 μM, 22 34%. 3. [ 3 H]MUS binding. H increased whole about 3-fold 6.0 15 μM. ~68% 2.3 12 Scatchard analysis revealed that due primarily increases number sites (Bmax values) no high affinity constants (Kd values). not additive. 4. [ 35 S]TBPS displaced [35S]TBPS from IC50 7.8 5.3 4.8 These inhibitory reversed by receptor blocker R5135 (10 nM), suggesting allosterically increase MUS complexes. 5. Two monophenols, anesthetic propofol (2,6-diisopropylphenol, P) anti-inflammatory diflunisal (2′,4′-difluoro-4-hydroxy-3-biphenyl carboxylic acid, D) also binding, potentiated although these monophenols smaller those M, P D completely 2,2′-biphenol inactive These, other preliminary experiments, suggest appropriate ortho (C2) para (C4) substitution GABA-potentiating activity phenols. 6. potentiation GABAergic neurotransmission is probably involved their previously reported anxiolytic central depressant effects.