HUMAN ERYTHROCYTE CHOLINE UPTAKE IN UREMIA - THE ROLE OF INTRACELLULAR SUBSTRATE AND AN INVESTIGATION INTO THE EFFECTS OF HEMODIALYSIS

1. Erythrocyte choline transport was studied in 10 haemodialysis patie nts immediately before and after a haemodialysis session and in 10 con trol subjects. Choline uptake was measured in erythrocytes from normal and uraemic patients after washing in vitro and subsequent incubation in autologous plasma, Amines present in uraemic plasma were examined for their effect on choline transport in normal erythrocytes. 2. NMR s pectroscopy was used to measure choline, trimethylamine and dimethylam ine in erythrocyte extracts from nine control subjects, 32 subjects wi th renal impairment and nine samples from haemodialysis patients. 3. T he increased choline influx in uraemic erythrocytes is significantly d ecreased by prior haemodialysis (mean V-max pre-dialysis 146+/-20 mu m ol h(-1)l(-1), post-dialysis 113+/-13 mu mol h(-1)l(-1) (P<0.005). Aft er in vitro washing there is a fall in V-max, and no longer any signif icant difference between pre- and post-dialysis samples. There remains a significant difference in the erythrocyte choline V-max between sam ples from patients with chronic renal failure and from normal subjects (P<0.005). 4. Human plasma was found to contain factors capable of in creasing choline uptake, Trimethylamine and dimethylamine were found t o inhibit choline uptake, Trimethylamine and trimethylamine-N-oxide tr ans-stimulated choline efflux, but the major transport substrate prese nt in erythrocyte extracts from all groups was choline, which was high er in those with renal impairment (71+/-10 mu mol/l) than in haemodial ysis patients (47+/-10 mu mol/l) and control subjects with normal rena l function (40+/-9 mu mol/l). 5. Our data suggest that erythrocyte cho line transport is increased in uraemia as a consequence of increased t ransporter number or activity, rather than the presence of intracellul ar substrate.