(−)-Indolactam V activates protein kinase C and induces changes in muscarinic receptor functions in SH-SY5Y human neuroblastoma cells

The effects of a synthetic protein kinase C (PKC) activator, (−)-indolactam V (ILV), were studied in SH-SY5Y human neuroblastoma cells. (−)-ILV induced a translocation of PKC from cytosol to plasma membrane and displaced 3H-phorbol dibutyrate binding in the micromolar range. In addition, (−)-ILV caused a decreased sensitivity of cells to muscarinic agonist-induced Ca 2+ mobilization measured with quin-2 and induced a down-regulation of cell surface muscarinic receptors. All the changes induced by (−)-ILV were similar in magnitude to those seen with the phorbol ester tetradecanoyl phorbol acetate (TPA). The results suggest that (−)-ILV is a full activator of PKC and a promising alternative to phorbol esters in studies on mechanism of actions of PKC.