Competitive Inhibition of P-aminohippurate Transport by Quinapril in Rabbit Renal Basolateral Membrane Vesicles

Overview

Journal J Pharmacokinet Biopharm

Specialty Pharmacology

Date 1999 Mar 31

PMID 10098100

Citations 2

Authors

W Akarawut

D E Smith

Affiliations

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Abstract

The mechanism of quinapril's interaction with the organic anion transporter was characterized by studying its effect on the transport of p-aminohippurate (PAH) in rabbit renal basolateral membrane vesicles (BLMV). Cis-inhibition studies demonstrated that quinapril was a specific and potent inhibitor of PAH. The Ki of quinapril was about 20 microM, a value similar to that of probenecid and eight-times lower than the K(m) value of 165 microM for PAH. Even though quinapril resulted in trans-inhibition of PAH uptake during counterflow studies, kinetic studies revealed that quinapril was a competitive inhibitor of PAH transport. This latter findings suggests that quinapril and PAH share a common binding site on the transporter. Overall, the results indicate that quinapril is a high-affinity inhibitor of the organic anion transporter in renal BLMV, and that drug-drug interactions may occur with other organic anions at the basolateral membrane of proximal cells.

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References

Wright S, Wunz T . Succinate and citrate transport in renal basolateral and brush-border membranes. Am J Physiol. 1987; 253(3 Pt 2):F432-9. DOI: 10.1152/ajprenal.1987.253.3.F432. View

Hopfer U, Nelson K, Perrotto J, Isselbacher K . Glucose transport in isolated brush border membrane from rat small intestine. J Biol Chem. 1973; 248(1):25-32. View

Talor Z, Gold R, Yang W, Arruda J . Anion exchanger is present in both luminal and basolateral renal membranes. Eur J Biochem. 1987; 164(3):695-702. DOI: 10.1111/j.1432-1033.1987.tb11182.x. View

Podevin R . Isolation of basolateral and brush-border membranes from the rabbit kidney cortex. Vesicle integrity and membrane sidedness of the basolateral fraction. Biochim Biophys Acta. 1983; 735(1):86-94. DOI: 10.1016/0005-2736(83)90263-8. View

Jorgensen P, Skou J . Purification and characterization of (Na+ + K+)-ATPase. I. The influence of detergents on the activity of (Na+ + K+)-ATPase in preparations from the outer medulla of rabbit kidney. Biochim Biophys Acta. 1971; 233(2):366-80. DOI: 10.1016/0005-2736(71)90334-8. View

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

Ullrich K, Rumrich G, Kloss S . Contraluminal organic anion and cation transport in the proximal renal tubule: V. Interaction with sulfamoyl- and phenoxy diuretics, and with beta-lactam antibiotics. Kidney Int. 1989; 36(1):78-88. DOI: 10.1038/ki.1989.164. View

REYNOLDS R, Wald H, McNAMARA P, Segal S . An improved method for isolation of basolateral membranes from rat kidney. Biochim Biophys Acta. 1980; 601(1):92-100. DOI: 10.1016/0005-2736(80)90516-7. View

Eveloff J . p-Aminohippurate transport in basal-lateral membrane vesicles from rabbit renal cortex: stimulation by pH and sodium gradients. Biochim Biophys Acta. 1987; 897(3):474-80. DOI: 10.1016/0005-2736(87)90444-5. View

10.

Sokol P, Holohan P, Ross C . The neurotoxins 1-methyl-4-phenylpyridinium and 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine are substrates for the organic cation transporter in renal brush border membrane vesicles. J Pharmacol Exp Ther. 1987; 242(1):152-7. View

11.

Noormohamed F, McNabb W, Lant A . Pharmacokinetic and pharmacodynamic actions of enalapril in humans: effect of probenecid pretreatment. J Pharmacol Exp Ther. 1990; 253(1):362-8. View

12.

Begg E, Robson R, Bailey R, Lynn K, Frank G, Olson S . The pharmacokinetics and pharmacodynamics of quinapril and quinaprilat in renal impairment. Br J Clin Pharmacol. 1990; 30(2):213-20. PMC: 1368220. DOI: 10.1111/j.1365-2125.1990.tb03767.x. View

13.

Hilden S, Johns C, Guggino W, Madias N . Techniques for isolation of brush-border and basolateral membrane vesicles from dog kidney cortex. Biochim Biophys Acta. 1989; 983(1):77-81. DOI: 10.1016/0005-2736(89)90382-9. View

14.

Kugler A, Olson S, Smith D . Tubular transport mechanisms of quinapril and quinaprilat in the isolated perfused rat kidney: effect of organic anions and cations. J Pharmacokinet Biopharm. 1996; 24(4):349-68. DOI: 10.1007/BF02353517. View

15.

Lazaruk K, Wright S . MPP+ is transported by the TEA(+)-H+ exchanger of renal brush-border membrane vesicles. Am J Physiol. 1990; 258(3 Pt 2):F597-605. DOI: 10.1152/ajprenal.1990.258.3.F597. View

16.

Schmitt C, Burckhardt G . p-Aminohippurate/2-oxoglutarate exchange in bovine renal brush-border and basolateral membrane vesicles. Pflugers Arch. 1993; 423(3-4):280-90. DOI: 10.1007/BF00374407. View

17.

Scalera V, Huang Y, Hildmann B, Murer H . A simple isolation method for basal-lateral plasma membranes from rat kidney cortex. Membr Biochem. 1981; 4(1):49-61. DOI: 10.3109/09687688109065422. View

18.

Shpun S, Evans K, Dantzler W . Interaction of alpha-KG with basolateral organic anion transporter in isolated rabbit renal S3 proximal tubules. Am J Physiol. 1995; 268(6 Pt 2):F1109-16. DOI: 10.1152/ajprenal.1995.268.6.F1109. View

19.

Holohan P, Ross C . Mechanisms of organic cation transport in kidney plasma membrane vesicles: 1. Countertransport studies. J Pharmacol Exp Ther. 1980; 215(1):191-7. View

20.

Jacolot A, Tod M, Petitjean O . Pharmacokinetic interaction between cefdinir and two angiotensin-converting enzyme inhibitors in rats. Antimicrob Agents Chemother. 1996; 40(4):979-82. PMC: 163242. DOI: 10.1128/AAC.40.4.979. View