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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
Author(s) -
Masson M.,
Spezzatti B.,
Chapman J.,
Battisti C.,
Baumann N.
Publication year - 1992
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490310112
Subject(s) - chlorpromazine , pharmacology , fibroblast , drug , chemistry , calmodulin , sphingomyelin , cholesterol , medicine , biochemistry , in vitro , enzyme
In this report we showed that calmodulin antagonists chlorpromazine (CPZ) and W‐7 (N‐[6‐ aminohexyl]‐5‐chloro‐1‐naphtalenesulfonamide), when added to fibroblast cell cultures, gave rise to a time‐ and dose dependent 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 (1‐[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.