Bumetanide-sensitive Na+/K+/Cl- transporter is stimulated by phorbol ester and different mitogens in quiescent human skin fibroblasts.
In this study we investigated the correlation between the mitogenic effect and stimulation of Rb+ (K+) fluxes in human skin fibroblasts treated by purified growth factors. Both K+ transporters, bumetanide-sensitive and ouabain-sensitive, are stimulated 2-3-fold after addition of either fetal calf serum or purified recombinant growth factors to quiescent G0/G1 human skin fibroblasts. Three groups of mitogens were compared: i) the phorbol ester 2-O-tetradecanoyl-phorbol-13-acetate (TPA); ii) growth factors that stimulate inositol phosphate hydrolysis and subsequently activate protein kinase C--fibroblast growth factor (FGF), platelet derived growth factor (PDGF), and alpha-thrombin; and iii) growth factors that do not activate kinase C--insulin-like growth factor-1 (IGF-1), and transforming like growth-factor-alpha (TGF-alpha). The three groups of mitogens stimulated human skin fibroblasts proliferation and Rb+ influxes in a similar dose-dependent fashion. The results indicate that both the bumetanide-sensitive and the ouabain-sensitive Rb+ fluxes are stimulated by protein kinase C-dependent and by the protein kinase C-independent pathways of the mitogenic signal.
Department of Medical Biophysics and Nuclear Medicine, Hadassah University Hospital, Jerusalem, Israel.
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D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects*; D002455:Cell Division / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D004261:DNA Replication; D005346:Fibroblast Growth Factors / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D012413:Rubidium / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000502:physiology; D016211:Transforming Growth Factor alpha / Q000502:physiology
D002352:Carrier Proteins; D002712:Chlorides; D006133:Growth Substances; D008565:Membrane Proteins; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D028021:Sodium-Potassium-Chloride Symporters; D016211:Transforming Growth Factor alpha; D002034:Bumetanide; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D012964:Sodium; D011493:Protein Kinase C; D013917:Thrombin; D012413:Rubidium; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium