Active Transport of Salicylate by Rat Jejunum

Fisher, R. B.

doi:10.1113/expphysiol.1981.sp002547

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…Various explanations have been applied for such deviations from the pH-partition hypothesis; including existence of the virtual pH (Brodie & Hogben 1957), the microclimate pH at the mucosal surface (Said et a1 1986;Schanker et a1 1958), and absorption of the ionized form through the paracellular pathway (Nogami & Matsuzawa 1961). Although all of these explanations are based on intestinal absorption by passive diffusion mechanisms, some previous results obtained by using intestinal perfusion methods suggest absorption of salicylic acid by a carrier-mediated mechanism (Fisher 1981;Takahata et a1 1986).…”

mentioning

confidence: 99%

pH-Dependent and Carrier-mediated Transport of Salicylic Acid Across Caco-2 Cells

Takanaga

Tamai

Tsuji

1994

Journal of Pharmacy and Pharmacology

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The transport of monocarboxylic acid drugs such as salicylic acid was examined in the human colon adenocarcinoma cell line, Caco-2 cells that possess intestinal epithelia-like properties. [14C]Salicylic acid transport was pH-dependent and appeared to follow the pH-partition hypothesis. However, 10 mM unlabelled salicylic acid significantly reduced the permeability coefficient of [14C]salicylic acid. Kinetic analysis of the concentration dependence of the permeation rate of salicylic acid across Caco-2 cells showed both saturable (Kt = 5.28 +/- 0.72 mM Jmax = 36.6 +/- 3.54 nmol min-1 (mg protein)-1) and nonsaturable (kd = 0.37 +/- 0.08 microL min-1 (mg protein)-1) processes. The permeation rate of [14C]salicylic acid was competitively inhibited by both acetic acid and benzoic acid, which were demonstrated in our previous studies to be transported in the carrier-mediated-transport mechanism which is responsible for monocarboxylic acids. Furthermore, certain monocarboxylic acids significantly inhibited [14C]salicylic acid transport, whereas salicylamide and dicarboxylic acids such as succinic acid did not. From these results, it was concluded that the transcellular transport of [14C]salicylic acid across Caco-2 cells is by the pH-dependent and carrier-mediated transport mechanism specific for monocarboxylic acids.

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confidence: 99%

pH-Dependent and Carrier-mediated Transport of Salicylic Acid Across Caco-2 Cells

Takanaga

Tamai

Tsuji

1994

Journal of Pharmacy and Pharmacology

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“…Caco-2, HT-29, and MDCK cells have been used with varying degrees of success [68][69][70][71]. They exhibit morphological features of small intestinal cells (e.g., tight intercellular junctions and microvilli) and express intestinal enzymes (e.g., aminopeptidases, esterases, sulfatases, and cytochrome P450 enzymes) and transporters (e.g., bile acid carrier, large neutral amino acid carrier, biotin carrier, monocarboxylic acid carrier, PEPT1, and p-glycoprotein) [71][72][73][74][75][76][77][78][79][80][81]. They exhibit morphological features of small intestinal cells (e.g., tight intercellular junctions and microvilli) and express intestinal enzymes (e.g., aminopeptidases, esterases, sulfatases, and cytochrome P450 enzymes) and transporters (e.g., bile acid carrier, large neutral amino acid carrier, biotin carrier, monocarboxylic acid carrier, PEPT1, and p-glycoprotein) [71][72][73][74][75][76][77][78][79][80][81].…”

Section: Caco-2 Cellsmentioning

confidence: 99%

Assessing the Absorption of New Pharmaceuticals

Hidalgo¹

2001

CTMC

166

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The advent of more efficient methods to synthesize and screen new chemical compounds is increasing the number of chemical leads identified in the drug discovery phase. Compounds with good biological activity may fail to become drugs due to insufficient oral absorption. Selection of drug development candidates with adequate absorption characteristics should increase the probability of success in the development phase. To assess the absorption potential of new chemical entities numerous in vitro and in vivo model systems have been used. Many laboratories rely on cell culture models of intestinal permeability such as, Caco-2, HT-29 and MDCK. To attempt to increase the throughput of permeability measurements, several physicochemical methods such as, immobilized artificial membrane (IAM) columns and parallel artificial membrane permeation assay (PAMPA) have been used. More recently, much attention has been given to the development of computational methods to predict drug absorption. However, it is clear that no single method will sufficient for studying drug absorption, but most likely a combination of systems will be needed. Higher throughput, less reliable methods could be used to discover 'loser' compounds, whereas lower throughput, more accurate methods could be used to optimize the absorption properties of lead compounds. Finally, accurate methods are needed to understand absorption mechanisms (efflux-limited absorption, carrier-mediated, intestinal metabolism) that may limit intestinal drug absorption. This information could be extremely valuable to medicinal chemists in the selection of favorable chemo-types. This review describes different techniques used for evaluating drug absorption and indicates their advantages and disadvantages.

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“…The adjacent cells adhere through tight junctions formed at the apical side of the monolayer. Caco-2 cells express several active transport systems that resemble those found in brush borders of the human small intestine, including carriers for the transport of amino acids − , nucleotides , bile acids − , vitamins , , oligopeptides − , and monocarboxylic acids , . Phospho-glycoprotein (P-gp), multidrug-resistance associated proteins (MRP), and breast-cancer resistance protein (BCRP) are also expressed in the cell membranes of Caco-2 cells and induce a basolateral-to-apical flux of xenobiotic compounds , .…”

Section: Introductionmentioning

confidence: 99%

Transport of Hop Bitter Acids across Intestinal Caco-2 Cell Monolayers

Cattoor¹,

Bracke

Deforce

et al. 2010

J. Agric. Food Chem.

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Several health-beneficial properties of hop bitter acids have been reported (inhibition of bone resorption and anticarcinogenic and anti-inflammatory activities); however, scientific data on the bioavailability of these compounds are lacking. As a first approach to study the bioavailability, the epithelial transport of hop alpha- and beta-acids across Caco-2 monolayers was investigated. Hop acids were added either to the apical or to the basolateral chamber and, at various time points, amounts transported to the receiving compartment were determined. The monolayer integrity control was performed by using marker compounds (atenolol and propranolol), transepithelial electrical resistance (TEER) measurement, and determination of the fluorescein efflux. The TEER and fluorescein efflux confirmed the preservation of the monolayer integrity. The membrane permeability of the alpha-acids (apparent permeability coefficients for apical to basolateral transport (P(appAB)) ranged from 14 x 10(-6) to 41 x 10(-6) cm/s) was determined to be substantially higher than that of the beta-acids (P(appAB) values ranging from 0.9 x 10(-6) to 2.1 x 10(-6) cm/s). Notably, the beta-acids exhibited significantly different bidirectional P(app) values with efflux ratios around 10. The involvement of carrier-mediated transport for beta-acids (active efflux pathway by P-gp, BCRP, and/or MRP-2 type efflux pumps) could be confirmed by transport experiments with specific inhibitors (verapamil and indomethacin). It appears that alpha-acids are efficiently absorbed, whereas the permeability of beta-acids is low. Limiting factors in the absorption of beta-acids could involve P-gp and MRP-2 type efflux transporters and phase II metabolism.

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Active Transport of Salicylate by Rat Jejunum

Cited by 7 publications

References 7 publications

pH-Dependent and Carrier-mediated Transport of Salicylic Acid Across Caco-2 Cells

pH-Dependent and Carrier-mediated Transport of Salicylic Acid Across Caco-2 Cells

Assessing the Absorption of New Pharmaceuticals

Transport of Hop Bitter Acids across Intestinal Caco-2 Cell Monolayers

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