Transepithelial transport of aliphatic carboxylic acids studied in Madin Darby canine kidney (MDCK) cell monolayers

Journal Article · Sun Apr 01 04:00:00 EDT 1990 · Pharmaceutical Research; (USA)

DOI:https://doi.org/10.1023/A:1015802918845· OSTI ID:6649812

Cho, M J; Adson, A; Kezdy, F J ^[1]

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1. Upjohn Company, Kalamazoo, MI (USA)

Transport of 14C-labeled acetic, propionic (PA), butyric, valeric, heptanoic (HA), and octanoic (OA) acids across the Madin Darby canine kidney (MDCK) epithelial cell monolayer grown on a porous polycarbonate membrane was studied in Hanks' balanced salt solution (HBSS) at 37{degrees}C in both apical-to-basolateral and basolateral-to-apical directions. At micromolar concentrations of solutes, metabolic decomposition was significant as evidenced by (14C)CO2 production during the OA transport. The apparent permeability (Pe) indicates that as lipophilicity increases, diffusion across the unstirred boundary layer becomes rate limiting. In support of this notion, transport of OA and HA was enhanced by agitation, showed an activation energy of 3.7 kcal/mol for OA, and resulted in identical Pe values for both transport directions. Analysis of Pe changes with varying alkyl chain length resulted in a delta G of -0.68 +/- 0.09 kcal/mol for -CH2-group transfer from an aqueous phase to the MDCK cells. When the intercellular tight junctions were opened by the divalent chelator EGTA in Ca2+/Mg2(+)-free HBSS, transport of the fluid-phase marker Lucifer yellow greatly increased because of paracellular leakage. PA transport also showed a significant increase, but OA transport was independent of EGTA. Although albumin also undergoes paracellular transport in the presence of EGTA and OA binds strongly to albumin, OA transport in EGTA solution was unchanged by albumin. These observations indicate that transmembrane transport is the major mechanism for lipophilic substances. The present study, together with earlier work on the transport of polar substances, shows that the MDCK cell monolayer is an excellent model of the transepithelial transport barrier.

• OSTI ID: 6649812
• Journal Information: Pharmaceutical Research; (USA), Journal Name: Pharmaceutical Research; (USA) Vol. 7:4; ISSN 0724-8741; ISSN PHREE
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ALCOHOLS
ANIMAL TISSUES
ANIMALS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CHELATING AGENTS
DOGS
EGTA
EPITHELIUM
GLYCOLS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KIDNEYS
LABELLED COMPOUNDS
LIPIDS
MAMMALS
MEMBRANE TRANSPORT
MEMBRANES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PERMEABILITY
PROTEINS
TISSUES
TRACER TECHNIQUES
VERTEBRATES