Calmodulin antagonist W-7 inhibits lysosomal sphingomyelinase activity in C6 glioma cells.
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) is known to be a potent calmodulin antagonist and inhibitor of calmodulin-dependent protein kinases. W-7 and 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) are inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases. In C6 glioma cells, W-7 and not H-7 inhibited dose-dependently acid sphingomyelinase, a result indicating the modulation of this lysosomal enzyme by a calmodulin-dependent system. Other lysosomal enzymes, such as beta-glucosidase, alpha-galactosidase, and arylsulfatase A, were unaffected by W-7 and H-7, a finding indicating a selective effect of W-7 on sphingomyelinase.
Masson
M
M
Unité de Neurobiologie Cellulaire Moléculaire et Clinique (INSERM U. 134), Paris, France.
Albouz
S
S
Boutry
J M
JM
Spezzatti
B
B
Castagna
M
M
Baumann
N
N
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003891:Desipramine / Q000494:pharmacology; D005910:Glioma / Q000201:enzymology*; D007546:Isoquinolines / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D010879:Piperazines / Q000494:pharmacology; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D007546:Isoquinolines; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013449:Sulfonamides; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D010727:Phosphoric Diester Hydrolases; D013108:Sphingomyelin Phosphodiesterase; D003891:Desipramine