Stereoselective and carrier-mediated transport of monocarboxylic acids across Caco-2 cells

Pharm Res. 1996 Dec;13(12):1828-32. doi: 10.1023/a:1016081007981.

Abstract

Purpose: To characterize the transport mechanism of monocarboxylic acids across intestinal epithelial cells by examining the stereoselectivity of the transcellular transport of several chiral monocarboxylic acids.

Methods: The transport of monocarboxylic acids was examined using monolayers of human adenocarcinoma cell line, Caco-2 cells.

Results: The permeability of L-[14C]lactic acid at a tracer concentration (1 microM) exhibited pH- and concentration-dependencies and was significantly greater than that of the D-isomer. The permeabilities of both L-/D-[14C]lactic acids involve saturable and nonsaturable processes; the saturable process showed a higher affinity and a lower capacity for L-lactic acid compared with the D-isomer, while no difference between the isomers was seen for the nonsaturable process. The transport of L-lactic acid was inhibited by chiral monocarboxylic acids such as (R)/ (S)-mandelic acids and (R)/(S)-ibuprofen in a stereoselective manner. Mutually competitive inhibition was observed between L-lactic acid and (S)-mandelic acid.

Conclusions: Some chiral monocarboxylic acids are transported across the intestinal epithelial cells in a stereoselective manner by the specific carrier-mediated transport mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Caco-2 Cells
  • Cell Membrane Permeability / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrogen-Ion Concentration
  • Ibuprofen / pharmacology
  • Kinetics
  • Lactates / metabolism*
  • Mandelic Acids / pharmacology
  • Sodium / metabolism
  • Stereoisomerism

Substances

  • Lactates
  • Mandelic Acids
  • Sodium
  • mandelic acid
  • Ibuprofen