Honokiol and magnolol selectively interact with GARAA receptor subtypes in vitro

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(A) receptor subtypes. This possibility was examined in the current study by H-3-muscimol and H-3-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 H-3-muscimol binding to various membrane preparations in nonsaturation binding assays. Honokiol and magnolol preferentially increased H-3-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 alpha (2) subunit containing combinations (with a maximum enhancement of 400-450% of control). This action was independent of the gamma subunit. In saturation binding assays, magnolol affected either the number of binding sites (ca. 4-fold on alpha (2) containing combinations) or the binding affinity (on alpha (1) containing combinations) of H-3-muscimol binding to various GABA(A) receptor subunit combinations, In contrast, honokiol increased only binding sites on alpha (2)beta (3)gamma (2s) and alpha (2)beta (3) combinations, but both the number of binding sites and the binding affinity on alpha (1)beta (2)gamma (2S) and alpha (1)beta (2) 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. Copyright (C) 2001 S. Kerger AG, Basel.