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.