Cellular MTT reduction distinguishes the mechanism of action of beta-amyloid from that of tachykinin receptor peptides.
Inhibition of the reduction of the redox dye 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide by rat phaeochromocytoma PC12 cells is a specific, early response to nanomolar concentrations of the beta-amyloid peptide fragment beta (25-35), and appears to be a reliable indicator of the mechanism of beta-amyloid toxicity. Neither selective tachykinin receptor agonists, nor tachykinin receptor peptide and non-peptide antagonists elicited such a response. Furthermore, tachykinin receptor peptides did not block the effects of beta-amyloid in PC12 cells, or in two other beta-amyloid-sensitive cell lines. These experimental model systems allow the mechanism of action of beta-amyloid to be distinguished from that of tachykinin receptor peptides, and prove that the neurotoxic action of beta-amyloid, as measured by the inhibition of cellular 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide reduction is not mediated by an interaction with tachykinin receptors.
Shearman
M S
MS
Merck Sharp & Dohme Research Laboratories. Neuroscience Research Centre, Harlow, Essex, UK. Mark_Shearman@Merck.com
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death; D004396:Coloring Agents; D004622:Embryo, Mammalian; D006801:Humans; D007668:Kidney; D009447:Neuroblastoma; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D018039:Receptors, Tachykinin / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D015320:Tachykinins / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D010446:Peptide Fragments; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue