Inhibitory effects of newly synthesized sulfonamide derivatives on calmodulin-dependent phosphodiesterase activity and their modulation of the external ATP-dependent permeability change in mammalian cultured cells.
External ATP causes a passive permeability change in several types of transformed cells and this change is further enhanced by calmodulin antagonists, such as trifluoperazine. However, such drugs also have nonspecific effects on membrane permeability. We have synthesized several new sulfonamide derivatives, which were found to inhibit calmodulin-dependent phosphodiesterase. The drugs also enhanced the ATP-dependent permeability change in CHO-K1 cells, but their effective concentration ranges were wider than those of previously known antagonists, and thus they would be useful for pharmacological use.
Kitagawa
T
T
Department of Chemistry, National Institute of Health, Tokyo, Japan.
Sato
S
S
Tamaki
T
T
Oda
T
T
Akamatsu
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D008322:Mammals; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
D002147:Calmodulin; D013449:Sulfonamides; D000255:Adenosine Triphosphate; D010727:Phosphoric Diester Hydrolases