The pH dependence of disobutamide-induced clear cytoplasmic vacuoles in cultured cells.
Cellular uptake of disobutamide (D), and clear cytoplasmic vacuoles (CCV) induction by D in cultured rat urinary bladder carcinoma cells were dependent on the culture medium pH. At pH 6.0-6.7, drug uptake was slow and no CCV formed in 24 hr. At pH 7.0-8.0, the rate of D uptake and early appearance of CCV were directly proportional to increased basicity. This was explained by the increasing fraction of un-ionized D molecules at increasing basicity of the culture medium. It is only these electrically neutral D molecules which can penetrate the lipoidal cell membrane to induce formation of CCV. Intracellular presence of D was demonstrated by mass spectrometry methods. The results indicate that D is incorporated intracellularly, that D and not its metabolite(s) is in cells, and suggest that CCV are a result of drug sequesteration.
D000818:Animals; D002460:Cell Line; D003470:Culture Media; D003593:Cytoplasm / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009940:Organoids / Q000648:ultrastructure*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D001749:Urinary Bladder Neoplasms / Q000648:ultrastructure*; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure*
D003470:Culture Media; D010880:Piperidines; C030153:disobutamide