Reciprocal effects of phenothiazines and naphthalene sulfonamides on the external ATP-dependent permeability change in Chinese hamster ovary cells.
External ATP causes a great increase in passive permeability to phosphorylated metabolites in several transformed cells, but not in untransformed cells. We have previously demonstrated that the external ATP-dependent permeability change was induced in Chinese hamster ovary cells, CHO-K1, only in the presence of a mitochondrial inhibitor (rotenone, KCN) or a cytoskeleton-attacking agent, vinblastine (Kitagawa, T. and Akamatsu, Y. Biochim. Biophys. Acta 649, 76-82 (1981); 734, 25-32 (1983]. A similar ATP-dependent permeability change was also induced in CHO cells when the cells were treated with 10-30 microM trifluoperazine. This permeability change, like the previously mentioned ones, was found to be reversible and the treated cells remained viable. The permeability change induced by ATP and trifluoperazine was independent of changes in cellular ATP concentration and this property was the same as that of the permeability change with external ATP and vinblastine. Since trifluoperazine is known to interact with calmodulin and to inhibit calmodulin-dependent cellular functions, these results may indicate that calmodulin associated with the cytoskeleton plays an important role in control of the permeability change, although nonspecific perturbation by the drug of the membranes cannot be ruled out. Chlorpromazine and a naphthalene sulfonamide, W-7, also induced an ATP-dependent permeability change. However, these drugs, like mitochondrial inhibitors, reduced the cellular ATP concentration to induce the permeability change. Thus, a clear difference in the action of these drugs in intact cells was also shown in this study. Possible mechanisms for the ATP-dependent permeability change in mammalian cells are discussed.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D010053:Ovary / Q000166:cytology / Q000187:drug effects*; D010640:Phenothiazines / Q000494:pharmacology*; D011190:Potassium Cyanide / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D010640:Phenothiazines; D013449:Sulfonamides; D012402:Rotenone; D014268:Trifluoperazine; D000266:Adenylyl Imidodiphosphate; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D000255:Adenosine Triphosphate; D011190:Potassium Cyanide; D002746:Chlorpromazine