Lithium stimulation of membrane-bound phospholipase C from PC12 cells exposed to nerve growth factor.
LiCl stimulated the formation of inositol monophosphate in PC12 cells that had been exposed to nerve growth factor (NGF) for 4-5 days. Half-maximal accumulation was observed at approximately 8 mM LiCl. Stimulation of formation of inositol bisphosphate plus inositol trisphosphate was half-maximal at approximately 1 mM LiCl. With membranes isolated from PC12 cells differentiated with NGF, the hydrolysis of added phosphatidylinositol 4,5-bisphosphate (PIP2) was stimulated by LiCl in a biphasic manner, with the first stimulation half-maximal at approximately 0.7 mM and the second half-maximal at approximately 15 mM LiCl. The apparent Km for PIP2 was lowered in the presence of 1.1 mM LiCl from approximately 200 to approximately 70 microM. Membranes from cells grown in the absence of NGF did not respond to LiCl. Although observations with intact cells are difficult to interpret without ambiguity, the results obtained with isolated membranes support our interpretation of the stimulatory action of lithium in the intact PC12 cells.
Volonté
C
C
Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853.
Racker
E
E
D000310:Adrenal Gland Neoplasms / Q000201:enzymology*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002712:Chlorides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D009414:Nerve Growth Factors / Q000494:pharmacology; D010673:Pheochromocytoma / Q000201:enzymology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D002712:Chlorides; D007295:Inositol Phosphates; D009414:Nerve Growth Factors; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D008094:Lithium; D010738:Type C Phospholipases; D018021:Lithium Chloride