Increases in Na/K pump numbers in isolated human lymphocytes exposed to lithium in vitro. Reversal by myo-inositol and by inhibitors of protein kinase C and the Na/H antiport.
Lithium (1-8 mM) caused a dose-dependent increase in the number of [3H]ouabain binding sites and in sodium/potassium (Na/K) pump activity in normal lymphocytes after incubation for 72 h. The increase in Na/K pump activity was due to an increase in the Vmax of the pump, with no change in the apparent affinity (Km) for potassium (rubidium). There was no change in the turnover number of the pump and the intracellular sodium concentration fell. The increase in [3H]ouabain binding sites was prevented by the addition of myo-inositol (10 mM), by inhibition of the protein kinase C with staurosporine (100 nM) and by inhibition of the Na/H antiport with dimethylamiloride (50 microM). These results suggest that the increase in Na/K pump activity caused by lithium is due to an increase in pump numbers and not due to increased activity of individual pumps or to an alteration in the affinity of the pumps for potassium. The increase in Na/K pump numbers and activity in lymphocytes exposed to lithium for 72 h may be related to altered Na/H antiport activity secondary to inhibition of phosphoinositol breakdown by lithium.
Jenkins
R J
RJ
MRC Unit, Radcliffe Infirmary, Oxford, U.K.
Aronson
J K
JK
Brearley
C J
CJ
D000328:Adult; D000470:Alkaloids / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000097:blood*; D005260:Female; D006801:Humans; D007294:Inositol / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010042:Ouabain / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012413:Rubidium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood*; D019311:Staurosporine
D000470:Alkaloids; D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D007294:Inositol; D010042:Ouabain; D000584:Amiloride; D008094:Lithium; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D019311:Staurosporine; D012413:Rubidium; D011188:Potassium