An anxiolytic agent, dihydrohonokiol-B, inhibits ammonia-induced increases in the intracellular Cl − of cultured rat hippocampal neurons via GABA c receptors

Abstract

The effects of an anxiolytic honokiol derivative, dihydrohonokiol-B (DHH-B) [3′-(2-propenyl)-5-propyl-(1,1′-biphenyl)-2,4′-diaol], on ammonia-induced increases in the intracellular Cl − concentration ([Cl −] i) were examined using primary cultured rat hippocampal neurons. DHH-B (1–100 ng/ml), but not an inactive isomer of honokiol, magnolol (100 ng/ml), dose-dependently inhibited the ammonia-induced increases in [Cl −] i without any changes in the control [Cl −] i. Such an effect of DHH-B was blocked by a gamma-aminobutylic acid A (GABA A) and GABA C Cl − channel blocker, 100 μM picrotoxin, and a GABA C receptor blocker, 10 μM (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid, but not by a GABA A receptor blocker, 10 μM bicuculline. Further, a GABA C receptor agonist, 200 μM cis-4-aminocrotonic acid, but not a GABA A receptor agonist, 10 μM muscimol, mimicked the effect of DHH-B. Thus, DHH-B appears to protect neurons from the ammonia-induced increases in [Cl −] i through GABA C receptor stimulation.