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.

Modifications of sphingomyelin and phosphatidylcholine metabolism by tricyclic antidepressants and phenothiazines.

Phenothiazines and tricyclic antidepressants, when added to culture medium, gave rise in several types of cells (C6 rat glioma cells and human fibroblasts), to a decrease in lysosomal sphingomyelinase activity. The effect of chlorpromazine and desipramine was dose dependent, and was observed after 3 hours of incubation with the drugs at concentrations ranging between 1 and 10 microM. In C6 glioma cell cultures, the decrease in sphingomyelinase activity was related to the clinical effectiveness of phenothiazines, tricyclic antidepressants and derivatives.

Desipramine elicits the expression of opiate receptors and sulfogalactosylceramide synthesis in rat C6 glioma cells.

In the course of our studies on lipidoses induced by amphiphilic drugs, we have investigated the ef- of desipramine, a tricyclic antidepressant, on glial cells in culture. We noted that the addition of desipramine to the culture medium of C6 glioma cells resulted in the modification of the lipid profile of the cell membranes. Of particular interest was the presence, in the desipramine-treated cells, of an additional lipid comigrating on thin layer chromatography with sulfogalactosylceramide (S-GalCer).

Effect of tricyclic antidepressants on sphingomyelinase and other sphingolipid hydrolases in C6 cultured glioma cells.

Cationic amphiphilic drugs, which include tricyclic antidepressants, have been shown to give rise to lipidoses under experimental conditions, with a general increase of lipids especially phospholipids. We report here an early and important decrease in sphingomyelinase activity in C6 glioma cells cultured in the presence of imipramine or desipramine at final concentrations of 0.01 and 0.

[Study of thesaurismosis induced by perhexiline maleate. Confirmation of experimental data].

Perhexiline maleate is an amphiphilic molecule. Along with many other drugs it is responsible for experimental and, in some instances, clinical lipidoses. Sphingomyelinase deficiency has been evidenced in cell cultures incubated with perhexiline maleate.