Phorbol ester TPA inhibits the stimulation of bumetanide-sensitive Na+/K+/Cl- transporter by different mitogens in quiescent BALB/c 3T3 mouse fibroblasts.
In this study we examined the effect of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the bumetanide-sensitive Na+/K+/Cl- transporter in quiescent BALB/c 3T3 cells. We have shown that exposure of quiescent BALB/c 3T3 cultures to phorbol ester did not inhibit the basal bumetanide-sensitive Rb+ influx or efflux. In fact, at high concentration (100 ng/ml), TPA slightly stimulated the bumetanide-sensitive Rb+ influx and efflux. However, when the quiescent cultures were stimulated by serum or by defined growth factors, the stimulated fraction of the bumetanide-sensitive Rb+ influx was drastically inhibited by exposure of the cells to the phorbol ester TPA. Based on the above findings, we propose that activation of protein kinase C by the phorbol ester TPA does not inhibit the Na+/K+/Cl- cotransport activity; however it does suppress only the growth-factors-stimulated fraction of the cotransport in quiescent BALB/c 3T3 cells. These data propose that activation of kinase C has a regulatory feedback effect on the stimulation of the Na+/K+/Cl- cotransport activity by growth factors.
Snyder
D
D
Department of Medical Biophysics and Nuclear Medicine, Hadassah University Hospital, Jerusalem, Israel.
Markus
M
M
Atlan
H
H
Panet
R
R
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology*; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D002352:Carrier Proteins; D006133:Growth Substances; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D028021:Sodium-Potassium-Chloride Symporters; D016211:Transforming Growth Factor alpha; D002034:Bumetanide; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013917:Thrombin; D012413:Rubidium; D013755:Tetradecanoylphorbol Acetate