We examined the intracellular Ca2+ response in primary cultured rat cortical neurons and human neuroblastoma SH-SY5Y cells by Fluo 3 fluorescence imaging analysis. In these two kinds of neuronal cells, honokiol and magnolol increased cytoplasmic free Ca2+ with a characteristic lag phase. The cytoplasmic free Ca2+ increase was independent of extracellular Ca2+, but dependent on activation of phospholipase C and inositol 1,4,5-triphosphate (IP3) receptors. These results suggest that honokiol and magnolol increase cytoplasmic free Ca2+ through a phospholipase C-mediated pathway, and that the release of Ca2+ from intracellular stores mainly contributes to the increase in cytoplasmic free Ca2+. Thus, honokiol and magnolol may be involved in a new activation mechanism closely associated with intracellular Ca2+ mobilization. (C) 2003 Elsevier B.V. All rights reserved.