Reabsorptive and secretory 5-methyltetrahydrofolate transport
pathways in cultured human proximal tubule cells.
Morshed, Khandoker M., and Kenneth E. McMartin.
Department of Pharmacology and Therapeutics, Louisiana State
University Medical Center, Shreveport, Louisiana 71130
APStracts 3:0224F, 1996.
Decreases in plasma folate levels leading to folate deficiency can
result from increased urinary loss of folate, due to changes in
either the renal reabsorption or secretion of folate. Hence, human
proximal tubule (HPT) cells were cultured on microporous membranes to
separate apical (AP) and basolateral (BL) domains and to assess the
transport of 5-methyltetrahydrofolate from AP to BL (i.e.,
reabsorptive) and BL to AP (secretory) directions. Cellular uptake of
[alpha]-methylglucoside occurred specifically from the AP direction
and transport of para-aminohippurate occurred more readily from the
BL direction, demonstrating cell polarity similar to that in vivo.
Under tight monolayer conditions, binding of folate to the AP
membrane occurred more readily from the AP direction, though AP
binding also occurred from the BL chamber. Intracellular transport
occurred equally from both AP and BL directions. When loaded from
either direction, folate was effluxed from HPT cells into both AP and
BL chambers. About 20-30% of the internalized substrate was converted
to nonfolate catabolites. Thus, HPT cells readily take up folate via
both the AP and BL membranes, metabolize it intracellularly and
secrete the products across both membranes. These studies suggest
that renal folate homeostasis is regulated bidirectionally.
Received 7 May 1996; accepted in final form 5 December 1996.
APS Manuscript Number F1134-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996