Characterization of human erythrocyte choline transport in chronic renal failure.

Abstract

BACKGROUND:

Membrane transport of choline cations is elevated in renal failure in erythrocytes and cerebral tissue but the origins and clinical importance of this are unknown.

METHODS:

The membrane transport changes have been characterized using erythrocytes from patients on maintenance haemodialysis (HD), patients on continuous ambulatory peritoneal dialysis (CAPD), and control subjects. Data were obtained from cells depleted of intracellular choline to create zero-trans (ZT) conditions for choline influx. [14C]-choline influx measurements provided a kinetic description of choline flux as the sum of a saturable transport system (defined by Vmax and Km) 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 polyamine putative uraemic toxins (putrescine, spermidine, spermine) were tested in control erythrocytes.

RESULTS:

Mean (SEM) Vmax (ZT) was increased in HD at 45.0 (3.0) mumol/l cells/h and in CAPD at 46.6 (2.5) mumol/l cells/h compared to controls (30.0 (2.0) mumol/l cells/h). Mean Km (ZT) was not significantly altered in HD or CAPD (HD: 6.1 (1.6) microM; CAPD: 5.5 (0.7) microM; control: 5.1 (0.9) microM). The sensitivity of choline transport to the inhibitors tested was not altered in HD. 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 microM choline the mean IC50 of quinine was 90 (9) microM in HD and 101 (13) microM in controls (n.s.). The ZT influx of 200 microM choline was not altered by any of the polyamines at concentrations up to 1.0 mM.

CONCLUSIONS:

Membrane choline transport in CRF remains protein-mediated and exhibits normal substrate and inhibitor affinities; high values of Vmax seem to occur through increased surface expression of an active normal choline transporter. Increases in plasma polyamines cannot explain the choline transport changes in CRF.

• Authors: S P Riley, N J Talbot, M J Ahmed, K Jouhal, B M Hendry
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 12 Issue 9 Pg. 1921-7 (Sep 1997) ISSN: 0931-0509 [Print] England
• PMID: 9306344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Cholinergic Agents
• Membrane Transport Proteins
• Polyamines
• choline transporter
• Hemicholinium 3
• Quinine
• Choline
• Ethylmaleimide

Topics

• Biological Transport (drug effects)
• Carrier Proteins (blood)
• Cell Membrane (metabolism)
• Choline (pharmacokinetics)
• Cholinergic Agents (pharmacology)
• Erythrocytes (metabolism)
• Ethylmaleimide (pharmacology)
• Female
• Hemicholinium 3 (pharmacology)
• Humans
• Kidney Failure, Chronic (blood)
• Kinetics
• Male
• Membrane Transport Proteins
• Middle Aged
• Peritoneal Dialysis, Continuous Ambulatory
• Polyamines (pharmacology)
• Quinine (pharmacology)
• Renal Dialysis