| Folate transport pathways regulate urinary excretion of 5-methyltetrahydrofolate in isolated perfused rat kidney. | |
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MedLine Citation:
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PMID: 8558307 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The reabsorption of 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) by the renal proximal tubule has an important role in the maintenance of plasma folate concentrations. However, the mechanism by which this vitamin traverses the renal epithelium remains to be determined. Studies in cultured cells have suggested that the folate receptor in association with a probenecid-sensitive anion carrier may be involved in the transmembrane transport of the vitamin. Because 5-CH3-H4PteGlu is reabsorbed and metabolized in the isolated perfused rat kidney (IPRK) in a smaller manner to in vivo models, the IPRK was used to evaluate pathways involved in folate reabsorption. Reabsorption of 5-CH3-H4PteGlu could not be saturated in the isolated perfused rat kidney, even at concentrations up to 2 mumol/L. Folic acid (PteGlu) was used as a competitive inhibitor of FR-dependent reabsorption of 5-CH3-H4PteGlu. When 5-CH3-H4PteGlu was maintained at 1 nmol/L (a concentration at which receptor-mediated transport should be maximal), PteGlu (up to 100 nmol/L) had no effect on reabsorption. The addition of probenecid (1 mmol/L) did not affect the reabsorption of 5-CH3-H4PteGlu but inhibited the fractional excretion of the anion para-aminohippurate. Probenecid also inhibited the urinary excretion of 5-CH3-H4PteGlu metabolites, indicating that reabsorbed 5-CH3-H4PteGlu was metabolized to products that were subsequently secreted into the urine by anion exchange pathways. The physiological importance of a folate receptor-mediated reabsorption of 5-CH3-H4PteGlu appears to be minor in the isolated perfused rat kidney, whereas nonspecific pathways appear to play a major role in the renal folate reabsorption. |
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Authors:
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R T Muldoon; D M Ross; K E McMartin |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of nutrition Volume: 126 ISSN: 0022-3166 ISO Abbreviation: J. Nutr. Publication Date: 1996 Jan |
Date Detail:
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Created Date: 1996-02-28 Completed Date: 1996-02-28 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0404243 Medline TA: J Nutr Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 242-50 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130-3932, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Biological Transport / physiology Chromatography, High Pressure Liquid Folic Acid / blood, pharmacokinetics* Kidney / metabolism*, physiology* Kidney Tubules, Proximal / metabolism, physiology Male Models, Biological Perfusion Probenecid / pharmacology Rats Rats, Sprague-Dawley Tetrahydrofolates / urine* |
| Grant Support | |
ID/Acronym/Agency:
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R01-AA05308/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Tetrahydrofolates; 134-35-0/5-methyltetrahydrofolate; 57-66-9/Probenecid; 59-30-3/Folic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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