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| RENAL ORGANIC-ACID TRANSPORT - UPTAKE BY RAT-KIDNEY SLICES OF A FURAN DICARBOXYLIC-ACID WHICH INHIBITS PLASMA-PROTEIN BINDING OF ACIDIC LIGANDS IN UREMIA |
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| Author(s): HENDERSON SJ, LINDUP WE |
| Source: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Volume: 263 Issue: 1 Pages: 54-60 Published: OCT 1992 |
| Times Cited: 31 References: 57 |
| Abstract: The furan dicarboxylic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (5-propyl FPA), accumulates in uremic plasma and inhibits the binding of various drugs and marker ligands that are organic acids. 5-Propyl FPA is excreted unchanged in human urine and active tubular secretion is likely to be involved because of its high affinity for albumin. The uptake of 5-propyl FPA by rat kidney slices has been measured and compared with that of p-aminohippurate (PAH). The mean (+/-S.D.) slice/medium ratio for uptake of 5-propyl FPA (76 muM) was 22.7 +/- 2.6 (n = 11) and for PAH (75 muM) was 15.9 +/- 3.2 (n = 9) after incubation for 90 min at 25-degrees-C. 5-Propyl FPA (149-829 muM) inhibited the uptake of PAH (77 muM) in a concentration-dependent manner, and likewise, PAH (150-830 muM) inhibited the uptake of 5-propyl FPA (77 muM). The mean apparent K(m) and V(max) values for the uptake of 5-propyl FPA were 194 +/- 125 muM and 55 +/- 28 nmol/g kidney/min, respectively, and 487 +/- 179 and 99 +/- 46 nmol/g kidney/min, respectively, for PAH. The kinetics of inhibition of uptake of PAH by 5-propyl FPA were mainly competitive. 5-Propyl FPA is thus likely to undergo active tubular secretion in a similar way to PAH, and this furan dicarboxylic acid, therefore, has the potential to inhibit the renal excretion of various drugs, drug conjugates and other endogenous organic acids. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV LIVERPOOL, DEPT PHARMACOL & THERAPEUT, POB 177, LIVERPOOL L69 3BX, ENGLAND |
| Publisher: WILLIAMS & WILKINS, 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 |
| Subject Category: Pharmacology & Pharmacy |
| IDS Number: JT987 |
| ISSN: 0022-3565 |
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