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Charge-dependent renal uptake of beta 2-microglobulin in conscious rats.

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Bernard, Alfred [UCL] Ouled Amor, A Lauwerys, Robert [UCL]

The influence of molecular charge on the tubular reabsorption of proteins was studied in conscious rats injected intravenously with beta 2-microglobulins of different isoelectric points (pI). Native human beta 2-microglobulin (pI 5.8), two anionized (pI 4.85 and 5.55) and three cationized derivatives (pI 7.2, 8.35 and 8.7) were used. The six forms of beta 2-microglobulin had a molecular radius between 15.7 and 15.9 A. The renal uptake was estimated by measuring the amount excreted in urine with a sensitive immunoassay. The ability of rat kidney to reabsorb beta 2-microglobulin was clearly related to the net charge of the protein. Increasing the pI of the protein significantly reduced the urinary excretion, whereas lowering it had the opposite effect. Anionization was particularly effective in reducing the beta 2-microglobulin uptake, since a decrease of the pI of one unit enhanced the urinary output by two orders of magnitude. This charge-dependency persisted when the tubular reabsorption of proteins was partly inhibited by lysozyme. By contrast, it was practically abolished by lysine, probably because the inhibitory effect of this amino acid on protein tubular reabsorption is not competitive. The administration of ammonium chloride in rats produced an immediate and transient elevation of rat beta 2-microglobulinuria. This phenomenon, which was partly inhibited by the subsequent administration of sodium bicarbonate, presumably results from a competition between the NH4+ ion and beta 2-microglobulin for tubular binding sites. These data support the hypothesis that proteins bind to the luminal membrane of tubular cells mainly via positively charged amino groups.

Document type Article de périodique (Journal article) – Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
Publication date 1992
Journal information "Scandinavian journal of clinical and laboratory investigation" - Vol. 52, no. 5, p. 415-23 (1992)
Peer reviewed yes
issn 0036-5513
Publication status Publié
Affiliation UCL - MD/ESP - Ecole de santé publique
MESH Subject Acidosis - chemically induced - urine ; Alkalosis - chemically induced - urine ; Ammonium Chloride ; Animals ; Bicarbonates ; Electrochemistry ; Electrophoresis, Agar Gel ; Female ; Humans ; Isoelectric Point ; Kidney - metabolism ; Rats ; Rats, Inbred Strains ; Sodium ; Sodium Bicarbonate ; beta 2-Microglobulin - chemistry - metabolism - urine
Links
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Bibliographic reference Bernard, Alfred ; Ouled Amor, A ; Lauwerys, Robert. Charge-dependent renal uptake of beta 2-microglobulin in conscious rats.. In: Scandinavian journal of clinical and laboratory investigation, Vol. 52, no. 5, p. 415-23 (1992)
Permanent URL http://hdl.handle.net/2078.1/13631