Calmodulin antagonists chlorpromazine and W-7 inhibit exogenous cholesterol esterification and sphingomyelinase activity in human skin fibroblast cultures. Similarities between drug-induced and niemann-pick type C lipidoses
✍ Scribed by M. Masson; B. Spezzatti; J. Chapman; C. Battisti; N. Baumann
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 461 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
In this report we showed that calmodulin antagonists chlorpromazine (CPZ) and W-7 (N-[6-aminohexyl]-5-chloro-l-naphtalenesulfonamide), when added to fibroblast cell cultures, gave rise to a time-and dosedependent decrease of sphingomyelinase activity. CPZ and W-7 also significantly inhibited LDL-and non-LDL-dependent cholesterol esterification. Addition of these drugs to cell culture medium mimicked what is observed in the genetic disease Niemann-Pick type C. H-7 (l-[5-isoquinonylsulfonyl]-2-methylpiperazine), an inhibitor of protein kinase C and cyclic nucleotide-dependent kinases, had no effect on sphingomyelinase and cholesterol ester formation. Thus the possibility of a modulation of cell sphingomyelin and cholesterol esters by a calmodulin-dependent second messenger system must be considered.