Yoshiki Koriyama, Matsumi Yamazaki, Kenzo Chiba and Tetsuro Mohri
Department of Biodynamics, Faculty of Pharmaceutical Sciences, Hokuriku
University, Kanazawa, Ishikawa 920-1181, Japan
Abstract: Neurotoxicity of b42 (20ﾊmM)
in cultured rat hippocampal neurons was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) reduction and lactate dehydrogenase (LDH) release methods
as quantitative assays of cell death, and both methods indicated that propentofylline
(PPF) had the ability to protect the neurons against the toxicity, although
these two assay methods revealed different mechanisms for the toxic effect
of b42. Promotion of the active exocytotic system
of the cells was suggested after treatment with b42
in the MTT assay and in determination of 9-aminoacridine (AA) excretion
from the preloaded cells after 24-h treatment with b42.
The promotion of AA exocytosis was blocked by the addition of PPF (20ﾊmg/ml).
The preventive effect of PPF on the neurotoxicity of b42
has been proposed to be caused by elevation of the intracellular level of
cAMP as a result of depression of the hydrolytic activity of cells.
Keywords: b-Amyloid protein, Hippocampal neuron,
Propentofylline, Exocytosis, cAMP