Renal folate absorption and the kidney folate binding protein. II. Microinfusion studies

1987 ◽  
Vol 252 (4) ◽  
pp. F757-F760 ◽  
Author(s):  
J. Selhub ◽  
S. Nakamura ◽  
F. A. Carone
Keyword(s):  
Folic Acid ◽  
Brush Border ◽  
Half Life ◽  
Binding Protein ◽  
Membrane Surface ◽  
Rapid Change ◽  
Acid Uptake ◽  
Folate Binding Protein ◽  
Acid Absorption ◽  
Folic Acid Absorption

Surface proximal convoluted tubules (PCT) in rats were microinfused in situ with [3H]folic acid to study the role of folate binding protein (FBP) in the kidney brush-border membrane for renal conservation and transport of folate [3H]folic acid absorption was linearly related to tubular length of PCT and occurred largely in this segment of the tubule. Unlabeled folate derivatives inhibited [3H]folic acid absorption, the extent of which was dependent on the type of unlabeled folate used and its concentration. At equivalent concentrations, inhibition was most effective with unlabeled folic acid, slightly lower than with 5-methyltetrahydrofolate and least effective with methotrexate. Comparisons between [3H]folic acid absorption before and after infusion of a saturating dose of unlabeled folic acid or repetitive injections of [3H]folic acid into the same tubular site revealed continuous and rapid regeneration of unsaturated folic acid uptake sites with an apparent half-life of 28.75 +/- 8.75 s. Determination of [3H] retained in the tubule at various periods after microinfusion of [3H]folic acid revealed slow cellular disappearance with an apparent half-life of 47.3 +/- 5.4 min. It is proposed that the brush-border FBP functions as a receptor of infused folic acid and that following the binding of the ligand the folic acid/FBP complex undergoes a rapid change that results in the internalization of folic acid and regeneration of unsaturated binding sites at the membrane surface. Internalized folic acid is slowly released into renal capillaries.

scholarly journals Affinity labelling of the folate-binding protein in pig intestine

1990 ◽  
Vol 267 (1) ◽  
pp. 249-252 ◽  
Author(s):  
A M Reisenauer
Keyword(s):  
Folic Acid ◽  
Brush Border ◽  
Binding Protein ◽  
Folate Binding Protein ◽  
Vacuum Filtration ◽  
Affinity Labelling ◽  
Hydroxysuccinimide Esters ◽  
Affinity Reagent ◽  
Filtration Technique ◽  
Specific Transport System

A specific transport system for folate and a high-affinity folate-binding protein have been identified in pig intestinal brush-border membranes. To determine if the binding protein plays a role in folic acid (PteGlu) uptake in to the cell, the inactivation of folate binding and transport by N-hydroxysuccinimide esters of folic acid (NHS-PteGlu) was compared. In addition, the number of brush-border proteins modified by the affinity reagent was assessed. Brush-border vesicles were incubated with various concentrations of NHS-PteGlu or NHS-methotrexate. Transport and binding of [3H]PteGlu by the vesicles were measured at 37 and 4 degrees C respectively by using the vacuum-filtration technique. NHS-methotrexate and NHS-PteGlu specifically inhibited PteGlu transport. Incubating the vesicles with 1 microM-NHS-PteGlu inactivated [3H]PteGlu transport by 60% and binding by 80%. Half-maximal inhibition of both transport and binding was observed at similar concentrations of the affinity reagent (0.05 and 0.07 microM-NHS-PteGlu respectively). Treating the vesicles with radiolabelled NHS-PteGlu followed by gel electrophoresis and autoradiography revealed a specifically labelled protein with an Mr of 56,000. These results indicate that the intestinal folate-binding and transport proteins are identical and that the function of the folate-binding protein is to transport folate into the cell.

Folic acid absorption in women with a history of pregnancy with neural tube defect

1995 ◽  
Vol 62 (4) ◽  
pp. 782-784 ◽  
Author(s):  
B A Davis ◽  
L B Bailey ◽  
J F Gregory ◽  
J P Toth ◽  
J Dean ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Neural Tube Defect ◽  
Acid Absorption ◽  
Folic Acid Absorption ◽  
History Of

scholarly journals Drugs and Folic Acid Absorption

1972 ◽  
Vol 63 (2) ◽  
pp. 353-357 ◽  
Author(s):  
Irwin H. Rosenberg
Keyword(s):  
Folic Acid ◽  
Acid Absorption ◽  
Folic Acid Absorption

Internalization and intracellular transport of folate-binding protein in rat kidney proximal tubule

1993 ◽  
Vol 264 (2) ◽  
pp. C302-C310 ◽  
Author(s):  
H. Birn ◽  
J. Selhub ◽  
E. I. Christensen
Keyword(s):  
Plasma Membrane ◽  
Proximal Tubule ◽  
Brush Border ◽  
Intracellular Transport ◽  
Brush Border Membrane ◽  
Specific Binding ◽  
Binding Protein ◽  
Rat Kidney ◽  
Folate Binding Protein

Folate-binding protein (FBP) is involved in folate reabsorption in the renal proximal tubule. Immunocytochemical studies have located FBP to the brush-border membrane, endocytic vacuoles, and dense apical tubules. We applied the same polyclonal antibody (anti-FBP) against FBP to investigate the dynamic relationship between FBP in the different compartments by microinjecting the antibody into rat kidney proximal tubules in situ. Specific binding of anti-FBP in vivo to the brush-border membrane was followed by fixation at various times. Protein A-gold labeling shows that anti-FBP is transported from endocytic invaginations into vacuoles followed by transport into dense apical tubules within 15 s. Thus FBP is rapidly internalized, and together with previous studies this study strongly suggests recycling of FBP back to the luminal plasma membrane through dense apical tubules. The results are consistent with reabsorption of folate through endocytosis of the FBP-folate complex followed by dissociation and recycling of FBP. When time is allowed there is a steady accumulation of FBP in dense apical tubules combined with an increase in surface density of the same compartment. A possible explanation involves partial inhibition of the fusion between dense apical tubules and plasma membrane because of the anti-FBP labeling of the receptor.

Role of sodium ion in transport of folic acid in the small intestine

1986 ◽  
Vol 251 (2) ◽  
pp. G218-G222 ◽  
Author(s):  
J. Zimmerman ◽  
J. Selhub ◽  
I. H. Rosenberg
Keyword(s):  
Small Intestine ◽  
Folic Acid ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Test Solution ◽  
Brush Border Membrane Vesicles ◽  
Acid Uptake ◽  
Folate Transport ◽  
Luminal Membrane

The effect of sodium on folate transport across the intestinal luminal membrane was analyzed using two techniques: the "influx" chamber and isolated brush-border membrane vesicles. Preincubation of tissue in Na+-free medium did not have a consistent effect on folic acid influx provided that Na+ was present in the test solution. Replacement of Na+ in the test solution by choline+ resulted in a significant reduction of folic acid influx. However, when intestinal sheets that had been equilibrated in Na+-free solution were exposed to test solution containing either Na+, Li+, K+, Rb+, Cs+, Tris+, or guanidinium+ as main cations, folic acid influx was not significantly decreased. Concentration-dependence studies showed that replacement of Na+ by Rb+ did not affect the saturable mechanism of folate transport. Rather, a decrease in nonsaturable folic acid uptake accounted for the slightly reduced influx observed in the presence of Rb+. Experiments with brush-border membrane vesicles revealed that methotrexate uptake was significantly higher in the presence of external Na+ than in the presence of K+, but was not different from uptake in the presence of K+ plus valinomycin. These data suggest that the saturable component of folate transport is not Na+ dependent, and nonsaturable transport of folic acid across the luminal membrane occurs in part through a conductive pathway that involves a negatively charged species of folate and a cation whose membrane permeability affects the rate of folate transport. The importance of Na+ in this process in vivo derives from the fact that Na+ is the most permeant cation available at the absorptive site in the small intestine.

scholarly journals Folic acid and folate binding protein in pregnancy.

1977 ◽  
Vol 23 (5) ◽  
pp. 447-453 ◽  
Author(s):  
Suvit AREEKUL ◽  
Petcharin YAMARAT ◽  
Manit VONGYUTHITHUM
Keyword(s):  
Folic Acid ◽  
Binding Protein ◽  
Folate Binding Protein ◽  
In Pregnancy
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