An anxiolytic agent, dihydrohonokiol-B, inhibits ammonia-induced increases in the intracellular Cl(-) of cultured rat hippocampal neurons via GABA(c) receptors.
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 microM picrotoxin, and a GABA(C) receptor blocker, 10 microM (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid, but not by a GABA(A) receptor blocker, 10 microM bicuculline. Further, a GABA(C) receptor agonist, 200 microM cis-4-aminocrotonic acid, but not a GABA(A) receptor agonist, 10 microM 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.
Irie
T
T
Department of Pharmacology, Kansai Medical University, 10-15 Fumizono-Cho, Moriguchi City, Osaka 570-8506, Japan.
Miyamoto
E
E
Kitagawa
K
K
Maruyama
Y
Y
Inoue
K
K
Inagaki
C
C
D000641:Ammonia / Q000378:metabolism / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005333:Fetus; D005456:Fluorescent Dyes; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006501:Hepatic Encephalopathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D022124:Hyperammonemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D014151:Anti-Anxiety Agents; D001713:Biphenyl Compounds; D002712:Chlorides; D005456:Fluorescent Dyes; D018755:GABA Agonists; D018756:GABA Antagonists; C087200:GABA-C receptor; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C417822:dihydrohonokiol; D000643:Ammonium Chloride; D005680:gamma-Aminobutyric Acid; D000641:Ammonia