Characterization of human erythrocyte choline transport in chronic renal failure
| Autor: | Nicholas J. Talbot, K Jouhal, S P Riley, M J Ahmed, B M Hendry |
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| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty Erythrocytes Cholinergic Agents Choline chemistry.chemical_compound Peritoneal Dialysis Continuous Ambulatory Hemicholinium-3 Renal Dialysis Internal medicine Phosphatidylcholine Polyamines medicine Humans Transplantation Quinine biology Membrane transport protein business.industry Cell Membrane Membrane Transport Proteins Biological Transport Hemicholinium 3 Middle Aged Membrane transport Choline transporter Kinetics Endocrinology chemistry Ethylmaleimide Nephrology biology.protein Kidney Failure Chronic Cholinergic Female Choline transport Carrier Proteins business |
| Zdroj: | Nephrology Dialysis Transplantation. 12:1921-1927 |
| ISSN: | 1460-2385 0931-0509 |
| Popis: | Key words: choline; chronic renal failure; erythrocyte;Background. Membrane transport of choline cations is membrane transport; polyamines; uraemiaelevated in renal failure in erythrocytes and cerebraltissue but the origins and clinical importance of thisare unknown.Methods. The membrane transport changes have been Introductioncharacterized using erythrocytes from patients onmaintenance haemodialysis (HD), patients on continu- Renal failure is associated with abnormal membraneous ambulatory peritoneal dialysis (CAPD), and con- transport of choline [1–5]. Increased transmembranetrol subjects. Data were obtained from cells depleted choline flux has been reported both in erythrocytesof intracellular choline to create zero-trans (ZT) condi- from patients with chronic renal failure and in cerebraltions for choline influx. [14C]-choline influx measure- synaptosomes isolated from a rat model of renal failurements provided a kinetic description of choline flux as [1,4]. The abnormalities appear to reverse within a fewthe sum of a saturable transport system (defined by days of successful renal transplantation [3]. MembraneV transport of choline is vitalfor the subsequent synthesismaxand Km) and an apparent diusion pathway.Inhibition of choline transport by hemicholinium-3 of choline-containing structural and bioactive phos-(HC-3), quinine and N-ethylmaleimide (NEM) has pholipids such as phosphatidylcholine, sphingomyelinbeen studied. Actions of three cationic polyamine and platelet-activating factor. Choline transport is alsoputative uraemic toxins (putrescine, spermidine, an essential prerequisite for the biosynthesis of acetyl-spermine) were tested in control erythrocytes. choline in cholinergic neurones. Abnormal cholineResults. Mean (SEM) V transport has been associated with altered T-cell func-max(ZT) was increased in HDat 45.0 (3.0) mmol/l cells/h and in CAPD at 46.6 (2.5) tion and cell proliferation and with a genetically deter-mmol/l cells/h compared to controls (30.0 (2.0) mmol/l mined cardiomyopathy [6–8]. Abnormal choline fluxcells/h). Mean K and metabolism has also been reported in Alzheimer’sm(ZT) was not significantly alteredin HD or CAPD (HD: 6.1 (1.6) mM; CAPD: 5.5 disease. Accordingly, changes in choline transport have(0.7) mM; control: 5.1 (0.9) mM). The sensitivity of been proposed as playing a role in some of the clinicalcholine transport to the inhibitors tested was not manifestations of uraemia, and particularly in neuro-altered in HD. 1.0 mM quinine, 2.0 mM NEM and logical, muscular, and immunological deficits [5].1.0 mM HC-3 caused 75–90% inhibition of transport At least three membrane transport systems for cho-in both HD and controls. For inhibition of ZT influx line transport have been identified on the basis ofof 25 mM choline the mean IC substrate anity, Na +dependence, tissue distribution,50of quinine was 90(9)mM in HD and 101 (13) mM in controls (n.s.). The and sensitivity to inhibition by hemicholinium-3ZT influx of 200 mM choline was not altered by any (HC-3) [1,9,10]. Genes for a yeast Na-independentof the polyamines at concentrations up to 1.0 mM. choline transporter and a rat Na-dependent cholineConclusions. Membrane choline transport in CRF transporter have been cloned and sequenced [11,12].remains protein-mediated and exhibits normal sub- In thispaper the abnormalmembrane choline transportstrate and inhibitor anities; high values of V in erythrocytes from patients with renal failure hasmaxseemto occur through increased surface expression of an been characterized with respect to the kinetics ofactive normal choline transporter. Increases in plasma transport and transporter sensitivity to inhibitors HC-3polyamines cannot explain the choline transport and quinine. The sensitivity of choline transport to thechanges in CRF. thiol-active agent N-ethylmaleimide (NEM) and toaltered Na+ have also been examined. In previouswork the kinetics of choline transport have been estim |
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