Anxiolytic agent, dihydrohonokiol-B, recovers amyloid beta protein-induced neurotoxicity in cultured rat hippocampal neurons.
The effects of anxiolytic honokiol derivative, dihydrohonokiol-B (DHH-B), on amyloid beta protein (Abeta(25-35), 10 nM)-induced changes in Cl(-)-ATPase activity, intracellular Cl- concentration ([Cl-]i) and glutamate neurotoxicity were examined in cultured rat hippocampal neurons. DHH-B (10 ng/ml) recovered Abeta-induced decrease in neuronal Cl(-)-ATPase activity without any changes in the activities of Na+/K+-ATPase and anion-insensitive Mg2+-ATPase. A GABA(C) receptor antagonist (1,2,5,6,-tetrahydropyridin-4-yl) methyl-phosphinic acid (TPMPA, 15 microM), inhibited the protective effects of DHH-B on Cl(-)-ATPase activity. DHH-B reduced Abeta-induced elevation of [Cl-]i as assayed using a Cl(-)-sensitive fluorescent dye, and prevented Abeta-induced aggravation of glutamate neurotoxicity. These data suggest that DHH-B exerts the neuroprotective action against Abeta through GABA(C) receptor stimulation.
Liu
Bing
B
Department of Pharmacology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.
Hattori
Naoki
N
Zhang
Nan-Yan
NY
Wu
Bo
B
Yang
Li
L
Kitagawa
Kaori
K
Xiong
Zheng-Mei
ZM
Irie
Takao
T
Inagaki
Chiyoko
C
D000251:Adenosine Triphosphatases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D027321:Anion Transport Proteins; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology*; D045022:Lactate Dehydrogenases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism
C476329:2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt; D016229:Amyloid beta-Peptides; D027321:Anion Transport Proteins; D014151:Anti-Anxiety Agents; D001713:Biphenyl Compounds; D002712:Chlorides; D013778:Tetrazolium Salts; C417822:dihydrohonokiol; D018698:Glutamic Acid; D045022:Lactate Dehydrogenases; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; C031652:anion-sensitive ATPases; D000254:Sodium-Potassium-Exchanging ATPase