Effect of cholesterol and dipalmitoyl phosphatidylcholine enrichment on the kinetics of Na-Li exchange of human erythrocytes.
The effects of cholesterol loading and depletion and of a 10% replacement of native phosphatidylcholine by dipalmitoyl phosphatidylcholine (di 16:0-PC) on kinetic properties of human red cell Na-Li exchange have been studied. Compared to control erythrocytes (cholesterol/phospholipid ratio (C/P = 0.8-0.9], Vmax of phloretin-sensitive Li uptake and of Li efflux stimulated by extracellular Na (Nao) were reduced by 15-30% in cholesterol-loaded red cells (C/P = 1.05-1.33). The apparent Km values for external Li (Lio) and for internal Li (Lii) were decreased by about one-third in these cells. Cholesterol depletion (C/P = 0.7) exerted opposite effects on the kinetics of Nao-dependent Li efflux. On augmenting C/P from 0.66 to 1.0, Vmax of Nao-dependent Li efflux was reduced by about 30%; increasing C/P above 1.0 caused no further lowering of Vmax.Li leakage rates monotonically decreased over the whole range of C/P ratios examined (0.66-1.3). This indicates that Na-Li exchange and Li leak are differentially affected by cholesterol. Incorporation of di 16:0-PC (replacement of 3% of total red cell phospholipids) caused similar kinetic alterations of Na-Li exchange as a rise in membrane cholesterol by 20-50%. Notably, selective incorporation of di 16:0-PC into the outer monolayer increased both intra- and extracellular Li binding affinities of Na-Li exchange and lowered its maximum velocity. Thus, both di 16:0-PC enrichment and cholesterol loading exerted an uncompetitive type of transport inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Physiologisches Institut, Universität München, Germany.
B
B
Engelmann
J
J
Duhm
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology*; D017920:Antiporters; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism / Q000493:pharmacokinetics* / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008094:Lithium / Q000378:metabolism / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism / Q000493:pharmacokinetics
D017920:Antiporters; D002352:Carrier Proteins; C045885:sodium-lithium countertransporter; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; D008094:Lithium; D012964:Sodium