![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
WH Dantzler, KK Evans and SH Wright
Department of Physiology, College of Medicine, University of Arizona, Tucson.
Kinetics of the first 15 s of para-aminohippurate (PAH) uptake across the basolateral membrane of single isolated S2 segments of rabbit proximal renal tubules and the effects of probenecid and cysteine conjugates on them were determined. For PAH uptake in control tubules, Kt (the concentration of PAH at 1/2 Jmax) was about 110 microM and Jmax (maximal rate of PAH transport) was about 6.5 pmol min-1 nl-1. In tubules preloaded with alpha-ketoglutarate (alpha-KG), thereby stimulating PAH/alpha-KG countertransport, Jmax doubled with little change in Kt. Probenecid cis-inhibited PAH uptake with an apparent Ki of about 13 to 15 microM whether or not the tubules were preloaded with alpha-KG. High probenecid concentrations cis-inhibited PAH uptake by > 98%, indicating that essentially all movement of PAH across the basolateral membrane is carrier mediated. Zwitterionic nephrotoxic cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and nontoxic cysteine conjugate, S-(2-benzothiazole)-L-cysteine (BTC) cis- inhibited PAH uptake (apparent Ki: approximately 86 microM for DCVC; approximately 37 microM for BTC) at least as effectively as their negatively charged N-acetyl derivatives (NAC-DCVC and NAC-BTC) (apparent Ki: approximately 310 microM for NAC-DCVC; approximately 35 microM for NAC-BTC). The inhibition by both DCVC and NAC-DCVC was competitive in nature. NAC-DCVC also cis-inhibited net transepithelial secretion of PAH by isolated, perfused S2 segments. The presence of DCVC and NAC-DCVC, as well as PAH itself, in the bathing medium trans- stimulated the 15 s efflux of PAH across the basolateral membrane of single S2 segments with oil-filled lumens. These data indicate that these cysteine conjugates and their N-acetyl derivatives, not only interact competitively with the PAH transporter, but are transported by it.
This article has been cited by other articles:
|
|
 |
|
  W. H. Dantzler Challenges and intriguing problems in comparative renal physiology J. Exp. Biol., February 15, 2005; 208(4): 587 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, C. E. Groves, A. Bahn, W. M. Barendt, M. D. Prado, M. Rodiger, V. Chatsudthipong, G. Burckhardt, and S. H. Wright Relative contribution of OAT and OCT transporters to organic electrolyte transport in rabbit proximal tubule Am J Physiol Renal Physiol, November 1, 2004; 287(5): F999 - F1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Zalups and S. Ahmad Homocysteine and the Renal Epithelial Transport and Toxicity of Inorganic Mercury: Role of Basolateral Transporter Organic Anion Transporter 1 J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2023 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sauvant, D. Hesse, H. Holzinger, K. K. Evans, W. H. Dantzler, and M. Gekle Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells Am J Physiol Renal Physiol, April 1, 2004; 286(4): F774 - F783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lungkaphin, V. Chatsudthipong, K. K. Evans, C. E. Groves, S. H. Wright, and W. H. Dantzler Interaction of the metal chelator DMPS with OAT1 and OAT3 in intact isolated rabbit renal proximal tubules Am J Physiol Renal Physiol, January 1, 2004; 286(1): F68 - F76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Groves, L. Munoz, A. Bahn, G. Burckhardt, and S. H. Wright Interaction of Cysteine Conjugates with Human and Rabbit Organic Anion Transporter 1 J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 560 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bahn, M. Knabe, Y. Hagos, M. Rodiger, S. Godehardt, D. S. Graber-Neufeld, K. K. Evans, G. Burckhardt, and S. H. Wright Interaction of the Metal Chelator 2,3-Dimercapto-1-propanesulfonate with the Rabbit Multispecific Organic Anion Transporter 1 (rbOAT1) Mol. Pharmacol., November 1, 2002; 62(5): 1128 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Chatsudthipong and P. Jutabha Effect of Steviol on para-Aminohippurate Transport by Isolated Perfused Rabbit Renal Proximal Tubule J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1120 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Zalups Molecular Interactions with Mercury in the Kidney Pharmacol. Rev., March 1, 2000; 52(1): 113 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Groves and M. N. Morales Chlorotrifluoroethylcysteine Interaction with Rabbit Proximal Tubule Cell Basolateral Membrane Organic Anion Transport and Apical Membrane Amino Acid Transport J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 555 - 561. [Abstract] [Full Text]
|
|
|
|
|
|
A. Shuprisha, R. M. Lynch, S. H. Wright, and W. H. Dantzler Real-time assessment of alpha -ketoglutarate effect on organic anion secretion in perfused rabbit proximal tubules Am J Physiol Renal Physiol, October 1, 1999; 277(4): F513 - F523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Edwards, E. J. Stack, and W. Trizna Transport of [3H]Losartan across Isolated Perfused Rabbit Proximal Tubule J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 38 - 42. [Abstract] [Full Text]
|
|
|
|
|
|
N. Apiwattanakul, T. Sekine, A. Chairoungdua, Y. Kanai, N. Nakajima, S. Sophasan, and H. Endou Transport Properties of Nonsteroidal Anti-Inflammatory Drugs by Organic Anion Transporter 1 Expressed in Xenopus laevis Oocytes Mol. Pharmacol., May 1, 1999; 55(5): 847 - 854. [Abstract] [Full Text]
|
|
|
|
|
|
V. Chatsudthipong, P. Jutabha, K. K. Evans, and W. H. Dantzler Effects of Inhibitors and Substitutes for Chloride in Lumen on p-Aminohippurate Transport by Isolated Perfused Rabbit Renal Proximal Tubules J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 993 - 1001. [Abstract] [Full Text]
|
|
|
|
|
|
C. E. GROVES, G. NOWAK, and M. MORALES Ochratoxin A Secretion in Primary Cultures of Rabbit Renal Proximal Tubule Cells J. Am. Soc. Nephrol., January 1, 1999; 10(1): 13 - 20. [Abstract] [Full Text]
|
|
|
|
|
|
R. K. Zalups, L. D. Parks, V. T. Cannon, and D. W. Barfuss Mechanisms of Action of 2,3-Dimercaptopropane-1-sulfonate and the Transport, Disposition, and Toxicity of Inorganic Mercury in Isolated Perfused Segments of Rabbit Proximal Tubules Mol. Pharmacol., August 1, 1998; 54(2): 353 - 363. [Abstract] [Full Text]
|
|
|
|
|
|
W. H. Dantzler, K. K. Evans, C. E. Groves, J. R. Welborn, J. North, J. L. Stevens, and S. H. Wright Relation of Cysteine Conjugate Nephrotoxicity to Transport by the Basolateral Organic Anion Transport System in Isolated S2 Segments of Rabbit Proximal Renal Tubules J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 52 - 60. [Abstract] [Full Text]
|
|
|
|
|
|
S. H. Wright, T. M. Wunz, J. North, and J. L. Stevens Na-Dependent Transport of S-(1,2-Dichlorovinyl)-L-Cysteine by Renal Brush-Border Membrane Vesicles J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 162 - 169. [Abstract] [Full Text]
|
|
|
|
|
|
J. R. Welborn, S. Shpun, W. H. Dantzler, and S. H. Wright Effect of alpha -ketoglutarate on organic anion transport in single rabbit renal proximal tubules Am J Physiol Renal Physiol, January 1, 1998; 274(1): F165 - F174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Lopez-Nieto, G. You, K. T. Bush, E. J.G. Barros, D. R. Beier, and S. K. Nigam Molecular Cloning and Characterization of NKT, a Gene Product Related to the Organic Cation Transporter Family That Is Almost Exclusively Expressed in the Kidney J. Biol. Chem., March 7, 1997; 272(10): 6471 - 6478. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
