The effect of a secreted form of β‐amyloid‐precursor protein on intracellular Ca 2+ increase in rat cultured hippocampal neurones

The effects of secreted forms of β‐amyloid‐precursor proteins (APP S s) on the intracellular Ca 2+ concentration ([Ca 2+ ] i ) were investigated in rat cultured hippocampal neurones. APP695 S , a secretory form of APP695, attenuated the increase in [Ca 2+ ] i evoked by glutamate. In addition, APP695 S itself evoked an increase in [Ca 2+ ] i in 1 or 2 day‐cultured hippocampal cells, but not in 7 to 13 day‐cultured cells. Eighty‐one percent of neurones which were immunocytochemically positive for microtubule‐associated protein 2 responded to APP695 S with an increase in [Ca 2+ ] i . APP695 S induced a transient rise in [Ca 2+ ] i even in the absence of extracellular Ca 2+ and produced an elevation in inositol‐1,4,5‐trisphosphate (IP 3 ) in a concentration‐dependent manner from 100 to 500 ng ml −1 . In the presence of extracellular Ca 2+ , APP695 S caused a transient rise in [Ca 2+ ] i followed by a sustained phase at high [Ca 2+ ] i , suggesting Ca 2+ entry from the extracellular space. The [Ca 2+ ] i elevation was mimicked by amino terminal peptides of APP S , but not by carboxy terminal peptides. These results taken together suggest that APP695 S induces an increase in [Ca 2+ ] i in hippocampal neurones through an IP 3 ‐dependent mechanism that changes according to the stage of development.British Journal of Pharmacology (1998) 123 , 1483–1489; doi: 10.1038/sj.bjp.0701712