POLYGODIAL INDUCES INOSITOL PHOSPHATE TURNOVER IN HUMAN NEUROBLASTOMASH-SY5Y CELLS

The pungent sesquiterpenoid unsaturated dialdehydes polygodial and iso velleral, have previously been shown to increase the intracellular fre e calcium concentration [Ca2+](i) in human neuroblastoma SH-SY5Y cells , partly by a release from intracellular Ca2+ stores, whereas the non- pungent compound epipolygodial, had no effect on the [Ca2+](i). In thi s study, we investigated the effect of isovelleral, polygodial and epi polygodial on inositol phosphate (IP) formation on the assumption that there might be a correlation between the release of intracellular Ca2 + and pungency of the compounds. It was found that polygodial induced IP mobilization in a concentration dependent way, whereas isovelleral had no effect on the IP formation in the SH-SY5Y cells. Phosphoinositi de (PPI) turnover was activated by epipolygodial, but only at concentr ations 40-fold higher than for polygodial, which emphasizes the import ance of the correct stereometry in the dialdehyde configuration for th e biological activity of polygodial. The polygodial-induced formation of IP1 was reduced by 71% under extracellular calcium-free conditions, which suggests feedback interactions between the IP formation and the increase in [Ca2+](i) to account for a periodic activation of phospho lipase C (PLC).