CHARACTERIZATION OF HUMAN ERYTHROCYTE CHOLINE TRANSPORT IN CHRONIC-RENAL-FAILURE

Background. Membrane transport of choline cations is elevated in renal failure in erythrocytes and cerebral tissue but the origins and clini cal importance of this are unknown. Methods. The membrane transport ch anges have been characterized using erythrocytes from patients on main tenance haemodialysis (HD), patients on continuous ambulatory peritone al dialysis (CAPD), and control subjects. Data were obtained from cell s depleted of intracellular choline to create zero-trans (ZT) conditio ns for choline influx. [C-14]-choline influx measurements provided a k inetic description of choline flux as the sum of a saturable transport system (defined by V-max and K-m) and an apparent diffusion pathway. Inhibition of choline transport by hemicholinium-3 (HC-3), quinine and N-ethylmaleimide (NEM) has been studied. Actions of three cationic po lyamine putative uraemic toxins (putrescine, spermidine, spermine) wer e tested in control erythrocytes. Results. Mean (SEM) V-max (ZT) was i ncreased in HD at 45.0 (3.0) mu mol/l cells/h and in CAPD at 46.6 (2.5 ) mu mol/l cells/h compared to controls (30.0 (2.0) mu mol/l cells/h). Mean K-m (ZT) was not significantly altered in HD or CAPD (HD: 6.1 (1 .6) mu M; CAPD: 5.5 (0.7) mu M; control: 5.1 (0.9) mu M). The sensitiv ity of choline transport to the inhibitors tested was not altered in H D. 1.0 mM quinine, 2.0 mM NEM and 1.0 mM HC-3 caused 75-90% inhibition of transport in both HD and controls. For inhibition of ZT influx of 25 mu M choline the mean IC50 of quinine was 90 (9) mu M in HD and 101 (13) mu M in controls (n.s.). The ZT influx of 200 mu M choline was n ot altered by any of the polyamines at concentrations up to 1.0 mM. Co nclusions. Membrane choline transport in CRF remains protein-mediated and exhibits normal substrate and inhibitor affinities; high values of V-max seem to occur through increased surface expression of an active normal choline transporter. Increases in plasma polyamines cannot exp lain the choline transport changes in CRF.