Honokiol and Magnolol Selectively Interact with GABAA Receptor Subtypes in vitro

Abstract

Honokiol and magnolol have been identified as modulators of the GABA_A receptors in vitro. Our previous study suggested a possible selectivity of honokiol and magnolol on GABA_Areceptor subtypes. This possibility was examined in the current study by ³H-muscimol and ³H-flunitrazepam binding assays on various rat brain membrane preparations and human recombinant GABA_A receptor subunit combinations expressed by the Sf-9/baculovirus system. Generally, honokiol and magnolol have a similar enhancing effect on ³H-muscimol binding to various membrane preparations in nonsaturation binding assays. Honokiol and magnolol preferentially increased ³H-muscimol binding to hippocampus compared to cortex and cerebellum (with a maximum enhancement of 400% of control). As for subunit combinations, honokiol and magnolol have a more potent enhancing effect on α₂ subunit containing combinations (with a maximum enhancement of 400–450% of control). This action was independent of the γ subunit. In saturation binding assays, magnolol affected either the number of binding sites (ca. 4-fold on α₂ containing combinations) or the binding affinity (on α₁ containing combinations) of ³H-muscimol binding to various GABA_A receptor subunit combinations. In contrast, honokiol increased only binding sites on α₂β₃γ_2s and α₂β₃ combinations, but both the number of binding sites and the binding affinity on α₁β₂γ_2S and α₁β₂ combinations. These results indicate that honokiol and magnolol have some selectivity on different GABA_A receptor subtypes. The property of interacting with GABA_A receptors and their selectivity could be responsible for the reported in vivo effects of these two compounds.