Low concentrations of ouabain induce vascular smooth muscle cell proliferation.
Ouabain is a well known inhibitor of the Na+ pump in all mammalian cells. We have demonstrated that ouabain at concentrations below those which inhibit the pump, i.e. 0.1 nM and 1.0 nM, induce proliferation of saphenous vein smooth muscle cells as measured by bromodeoxyuridine (BrdU) uptake. Ouabain at these low concentrations also activated MAPK. Proliferating concentrations of the drug did not increase levels of Ca(i)2+, suggesting no effect of this ion in the process. In addition, incubation of the cells in low levels of K+, which has been shown to inhibit the pump, had no effect on proliferation. These data show that low concentrations of ouabain that do not inhibit the Na+ pump can activate proliferation of vascular smooth muscle cells, suggesting that the pump complex may act as a transducing receptor.
Aydemir-Koksoy
A
A
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
Allen
J C
JC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004285:Dogs; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D012501:Saphenous Vein / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D010042:Ouabain; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium