(-)-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 Ca2+ 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.
Department of Biochemistry and Pharmacy, Abo Academy, Finland.
J
J
Heikkilä
K E
KE
Akerman
D002118:Calcium / Q000502:physiology; D002451:Cell Compartmentation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007769:Lactams / Q000494:pharmacology*; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007211:Indoles; D007769:Lactams; D011976:Receptors, Muscarinic; D015240:Phorbol 12,13-Dibutyrate; C043969:indolactam V; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium