Transcellular Transport of Benzoic Acid Across Caco-2 Cells by a PH-dependent and Carrier-mediated Transport Mechanism

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 1994 Jan 1

PMID 8140053

Citations 25

Authors

A Tsuji

H Takanaga

I Tamai

T Terasaki

Affiliations

Soon will be listed here.

Abstract

The pH-dependent transcellular transport of [14C]benzoic acid across a Caco-2 cell monolayer is shown to be mediated by a monocarboxylic acid-specific carrier-mediated transport system, localized on the apical membrane. Evidence for the carrier-mediated transport of benzoic acid includes (a) the significant temperature and concentration dependence, (b) the metabolic energy dependence, (c) the inhibition by unlabeled benzoic acid and other monocarboxylic acids, (d) countertransport effects on the uptake of [14C]benzoic acid, and (e) effects of a proteinase (papain) and amino acid-modifying reagents. Furthermore, since carbonylcyanide p-trifluoromethoxyphenylhydrazone and nigericin significantly inhibited the transport of [14C]benzoic acid, the direct driving force for benzoic acid transport is suggested to be the inwardly directed proton gradient. From these results, together with previous observations using intestinal brush border membrane vesicles, the pH dependence of the transcellular transport of certain organic weak acids across Caco-2 cells is considered to result mainly from a proton gradient-dependent, carrier-mediated transport mechanism, rather than passive diffusion according to the pH-partition theory.

Citing Articles

Immunohistochemical and functional characterization of peptide, organic cation, neutral and basic amino acid, and monocarboxylate drug transporters in human ocular tissues.

Kadam R, Vooturi S, Kompella U Drug Metab Dispos. 2012; 41(2):466-74.

PMID: 23169611 PMC: 3558866. DOI: 10.1124/dmd.112.045674.

Transporter targeted gatifloxacin prodrugs: synthesis, permeability, and topical ocular delivery.

Vooturi S, Kadam R, Kompella U Mol Pharm. 2012; 9(11):3136-46.

PMID: 23003105 PMC: 3926802. DOI: 10.1021/mp300245r.

Salicylic acid transport in Ricinus communis involves a pH-dependent carrier system in addition to diffusion.

Rocher F, Chollet J, Legros S, Jousse C, Lemoine R, Faucher M Plant Physiol. 2009; 150(4):2081-91.

PMID: 19493970 PMC: 2719138. DOI: 10.1104/pp.109.140095.

Intestinal absorption of miltefosine: contribution of passive paracellular transport.

Menez C, Buyse M, Dugave C, Farinotti R, Barratt G Pharm Res. 2007; 24(3):546-54.

PMID: 17252190 DOI: 10.1007/s11095-006-9170-7.

Salicylic acid, an ambimobile molecule exhibiting a high ability to accumulate in the phloem.

Rocher F, Chollet J, Jousse C, Bonnemain J Plant Physiol. 2006; 141(4):1684-93.

PMID: 16778012 PMC: 1533928. DOI: 10.1104/pp.106.082537.

References

Tsuji A, Simanjuntak M, Tamai I, Terasaki T . pH-dependent intestinal transport of monocarboxylic acids: carrier-mediated and H(+)-cotransport mechanism versus pH-partition hypothesis. J Pharm Sci. 1990; 79(12):1123-4. DOI: 10.1002/jps.2600791217. View

Artursson P, Karlsson J . Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem Biophys Res Commun. 1991; 175(3):880-5. DOI: 10.1016/0006-291x(91)91647-u. View

Titus E, Ahearn G . Short-chain fatty acid transport in the intestine of a herbivorous teleost. J Exp Biol. 1988; 135:77-94. DOI: 10.1242/jeb.135.1.77. View

Ho N, Higuchi W, Turi J . Theoretical model studies of drug absorption and transport in the GI tract. 3. J Pharm Sci. 1972; 61(2):192-7. DOI: 10.1002/jps.2600610210. View

Dantzig A, Bergin L . Uptake of the cephalosporin, cephalexin, by a dipeptide transport carrier in the human intestinal cell line, Caco-2. Biochim Biophys Acta. 1990; 1027(3):211-7. DOI: 10.1016/0005-2736(90)90309-c. View

Hogerle M, WINNE D . Drug absorption by the rat jejunum perfused in situ. Dissociation from the pH-partition theory and role of microclimate-pH and unstirred layer. Naunyn Schmiedebergs Arch Pharmacol. 1983; 322(4):249-55. DOI: 10.1007/BF00508339. View

Grillo F, Aronson P . Inactivation of the renal microvillus membrane Na+-H+ exchanger by histidine-specific reagents. J Biol Chem. 1986; 261(3):1120-5. View

Hilgers A, Conradi R, Burton P . Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa. Pharm Res. 1990; 7(9):902-10. DOI: 10.1023/a:1015937605100. View

Turner R, George J . Evidence for two disulfide bonds important to the functioning of the renal outer cortical brush-border membrane D-glucose transporter. J Biol Chem. 1983; 258(6):3565-70. View

10.

Simanjuntak M, Terasaki T, Tamai I, Tsuji A . Participation of monocarboxylic anion and bicarbonate exchange system for the transport of acetic acid and monocarboxylic acid drugs in the small intestinal brush-border membrane vesicles. J Pharmacobiodyn. 1991; 14(9):501-8. DOI: 10.1248/bpb1978.14.501. View

11.

Yamaoka K, Tanigawara Y, Nakagawa T, Uno T . A pharmacokinetic analysis program (multi) for microcomputer. J Pharmacobiodyn. 1981; 4(11):879-85. DOI: 10.1248/bpb1978.4.879. View

12.

Simanjuntak M, Tamai I, Terasaki T, Tsuji A . Carrier-mediated uptake of nicotinic acid by rat intestinal brush-border membrane vesicles and relation to monocarboxylic acid transport. J Pharmacobiodyn. 1990; 13(5):301-9. DOI: 10.1248/bpb1978.13.301. View

13.

Watson A, Levine S, Donowitz M, Montrose M . Kinetics and regulation of a polarized Na(+)-H+ exchanger from Caco-2 cells, a human intestinal cell line. Am J Physiol. 1991; 261(2 Pt 1):G229-38. DOI: 10.1152/ajpgi.1991.261.2.G229. View

14.

Hughson E, Hopkins C . Endocytic pathways in polarized Caco-2 cells: identification of an endosomal compartment accessible from both apical and basolateral surfaces. J Cell Biol. 1990; 110(2):337-48. PMC: 2115999. DOI: 10.1083/jcb.110.2.337. View

15.

Harig J, SOERGEL K, Barry J, Ramaswamy K . Transport of propionate by human ileal brush-border membrane vesicles. Am J Physiol. 1991; 260(5 Pt 1):G776-82. DOI: 10.1152/ajpgi.1991.260.5.G776. View

16.

Hidalgo I, Borchardt R . Transport of a large neutral amino acid (phenylalanine) in a human intestinal epithelial cell line: Caco-2. Biochim Biophys Acta. 1990; 1028(1):25-30. DOI: 10.1016/0005-2736(90)90261-l. View

17.

Said H, Blair J, Lucas M, Hilburn M . Intestinal surface acid microclimate in vitro and in vivo in the rat. J Lab Clin Med. 1986; 107(5):420-4. View

18.

Miyamoto Y, Ganapathy V, Leibach F . Identification of histidyl and thiol groups at the active site of rabbit renal dipeptide transporter. J Biol Chem. 1986; 261(34):16133-40. View

19.

WINNE D . Unstirred layer, source of biased Michaelis constant in membrane transport. Biochim Biophys Acta. 1973; 298(1):27-31. DOI: 10.1016/0005-2736(73)90005-9. View

20.

Aronson P, Suhm M, Nee J . Interaction of external H+ with the Na+-H+ exchanger in renal microvillus membrane vesicles. J Biol Chem. 1983; 258(11):6767-71. View