Inhibition of the membrane transport of folates by anions retained in uremia

J. Charles Jennette, I. David Goldman

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Previous studies from this laboratory indicated that inorganic and organic anions inhibit the unidirectional influx and net transport of the folate analog methotrexate in mammalian cells. Studies were undertaken to establish whether anions retained in uremia might inhibit the membrane transport of folates. Methotrexate was utilized as a model folate compound and its transport was determined in the Ehrlich ascites tumor cell. Influx of methotrexate was inhibited when cells were suspended into sera or ultrafiltrates of sera (pH adjusted to 7.4 by regulation of Pco2) from uremic patients, an effect that was decreased after the patient underwent hemodialysis or peritoneal dialysis. The inhibitory effect of uremic sera correlated well with the level of retained anions as estimated from the "anion gap," but could not be related to changes in osmolality, blood urea nitrogen (BUN), sodium, potassium, calcium, or magnesium. While inhibiting the influx of methotrexate, inorganic anions did not displace methotrexate from albumin binding sites. Anionic inhibition of the membrane transport of 5-methyl [14C] tetrahydrofolate was also demonstrated and this was shown to be accompanied by a depression in the rate of incorporation of the labeled 14C moiety into nucleic acids and protein. The data suggest that transport of folates is imparied in uremia and raises the possibility that whatever the measured blood folate level in the uremic individual with retained anions, the rate of uptake of folates into folate-dependent tissues which this blood folate level will sustain may be reduced.

Original languageEnglish (US)
Pages (from-to)834-843
Number of pages10
JournalThe Journal of Laboratory and Clinical Medicine
Volume86
Issue number5
StatePublished - 1975
Externally publishedYes

Fingerprint

Uremia
Folic Acid
Anions
Membranes
Methotrexate
Blood
Serum
Cells
Ehrlich Tumor Carcinoma
Dialysis
Acid-Base Equilibrium
Blood Urea Nitrogen
Peritoneal Dialysis
Osmolar Concentration
Magnesium
Nucleic Acids
Renal Dialysis
Urea
Tumors
Albumins

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Inhibition of the membrane transport of folates by anions retained in uremia. / Jennette, J. Charles; Goldman, I. David.

In: The Journal of Laboratory and Clinical Medicine, Vol. 86, No. 5, 1975, p. 834-843.

Research output: Contribution to journalArticle

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