Phorbol ester TPA inhibits the stimulation of bumetanide-sensitive Na+/K+/Cl– transporter by different mitogens in quiescent BALB/c 3T3 mouse fibroblasts

✍ Scribed by David Snyder; Miriam Markus; Henri Atlan; Rivka Panet

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 728 KB
• Volume: 146
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041460318

✦ Synopsis

In this study we examined the effect of the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) on the burnetanide-sensitive Na+iK+iCI-transporter in quiescent BALBic 3T3 cells. We have shown that exposure of quiescent BALBic 3T3 cultures to phorbol ester did not inhibit the basal burnetanide-sensitive Rb+ influx or efflux. In fact, at high concentration (100 ngiml), 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 burnetanide-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+iK+iCI -cotransport activity; however it does suppress only the growth-factors-stimulated fraction of the cotransport in quiescent BALBic 3T3 cells. These data propose that activation of kinase C has a regulatory feedback effect on the stimulation of the Na+iK+lCI-cotransport activity by growth factors.

Recent observations have shown that several activators of protein kinase C are unable to stimulate ion fluxes in several cell lines, including BALB/c 3T3 cells