title: Transport by the (Na+,K+) ATPase: modulation by differentiation inducers and inhibition of protein synthesis in the MDCK kidney epithelial cell line.
abstract: MDCK kidney epithelial cell cultures exposed to the differentiation inducer hexamethylene bisacetamide (HMBA) for 24 hours exhibited a 50% decrease in transport activity per (Na+,K+)-ATPase molecule (turnover number) but an unchanged number of pump sites (Kennedy and Lever, 1984). Inhibition of protein synthesis by either 10 microM cycloheximide or 2 microM emetine blocked the inhibitory effects of HMBA on Na+/K+ pump efficiency assessed by measurements of [3H]-ouabain binding to intact cells, (Na+,K+) ATPase activity of detergent-activated cell extracts, and ouabain-sensitive Rb+ uptake. In the absence of inducer treatment, inhibition of protein synthesis increased Na+/K+ pump turnover number by twofold while maintaining Na+/K+ pump activity per cell at a constant level. Intracellular Na+ levels were decreased after cycloheximide treatment; therefore, pump stimulation was not due to substrate effects. Furthermore, cycloheximide effects of Rb+ uptake could be dissociated from effects on tight junctions. These observations suggest that the transport activity of the (Na+,K+) ATPase is tightly regulated by factors dependent on protein synthesis.
authors.forename: B G
authors.initials: BG
authors.lastname: Kennedy
authors.forename: J E
authors.initials: JE
authors.lastname: Lever
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004285:Dogs; D004640:Emetine / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D010042:Ouabain / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D000081:Acetamides; D007473:Ion Channels; D011506:Proteins; D010042:Ouabain; D003513:Cycloheximide; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; C014026:hexamethylene bisacetamide; D004640:Emetine