Phorbol esters augment polyamine transport by influencing Na(+)-K+ pump in murine leukemia cells.

Abstract

In this report, we elucidate the role of Na(+)-K+ pump in the regulation of polyamine spermidine (Spd) transport in murine leukemia (L 1210) cells in culture. Ouabain, known to bind extracellularly to the alpha-subunit of the Na(+)-K+ pump, inhibits the pump activity. The L 1210 cells were found to possess ouabain binding sites at 7.5 fmol/10(6) cells. Ouabain significantly inhibited the Spd uptake in a dose-dependent manner. The maximum inhibition of Spd uptake by ouabain was observed beyond 200 microM. Spd transport was inversely correlated with the [3H]ouabain binding to L 1210 cells: an increase in the saturation of ouabain binding to L 1210 cells resulted in a decrease of the Spd uptake process. Treatment of L 1210 cells with protein kinase C activator phorbol esters increased the Spd transport and, also, ouabain-sensitive 86Rb+ uptake, a measure of the activity of the Na(+)-K+ pump. H-7, a protein kinase C inhibitor, significantly inhibited the ouabain-sensitive 86Rb+ uptake by L 1210 cells. Phorbol esters stimulated the level, but not the rate, of 22Na+ influx. Addition of H-7 to L 1210 cells inhibited the 22Na+ influx process. A concomitant phorbol ester-induced increase in 22Na+ influx, [14C]Spd uptake, together with the functioning of Na(+)-K+ pump, indicates the role of the "Na+ cycle" in the regulation of the polyamine transport process.

• Authors: N A Khan, V Quemener, J P Moulinoux
• Journal: Experimental cell research (Exp Cell Res) Vol. 199 Issue 2 Pg. 378-82 (Apr 1992) ISSN: 0014-4827 [Print] United States
• PMID: 1312010 (Publication Type: Journal Article)

Chemical References

• Isoquinolines
• Piperazines
• Polyamines
• Ouabain
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• Sodium
• Protein Kinase C
• Sodium-Potassium-Exchanging ATPase
• Rubidium
• Tetradecanoylphorbol Acetate

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• Animals
• Biological Transport (drug effects)
• Isoquinolines (pharmacology)
• Leukemia L1210 (metabolism)
• Mice
• Ouabain (metabolism, pharmacology)
• Piperazines (pharmacology)
• Polyamines (metabolism)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Rubidium (metabolism)
• Sodium (metabolism)
• Sodium-Potassium-Exchanging ATPase (drug effects)
• Tetradecanoylphorbol Acetate (pharmacology)