Organic anion transport apical transporters

D. Kobayashi, T. Nozawa, K. Imai, J. Nezu, A. Tsuji, and I. Tamai. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J Pharmacol Exp Ther 306 703-708 (2003). 

Ekaratanawong S, Anzai N, Jutabha P, Miyazaki H, Noshiro R, Takeda M, Kanai Y, Sophasan S, Endou H. Human organic anion transporter 4 is a renal apical organic anion/dicarboxylate exchanger in the proximal tubules. J Pharmacol Sci 2004 94 297-304. 

Van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG. The MRP4/ ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol 2002 13 595-603. 

Sai Y, Kaneko Y, Ito S, et al. Predominant contribution of organic anion transporting polypeptide OATP-B (OATP2B1) to apical uptake of estrone-3-sulfate by human intestinal Caco-2 cells. Drug Metab Dispos 2006 34 1423-1431. 

Anzai N, Jutabha P, Enomoto A, et al. Functional characterization of rat organic anion transporter 5 (Slc22al9) at the apical membrane of renal proximal tubules. J Pharmacol Exp Ther 2005 315 534—544. 

NPTl and MPR2 are two organic anion transporters which have been identified by molecular biology techniques, and which, in the kidney, were localized to the apical membrane of proximal tubule. They might be involved in organic anion secretion. 

Masuda S,Takeuchi A, Saito El, ElashimotoY, Inui K. Functional analysis of rat renal organic anion transporter OAT-Kl bidirectional methotrexate transport in apical membrane. FEES Letters 1999 459 128-132. 

Uptake of these cysteine and GSH conjugates occurs across the apical membrane through Na -dependent and -independent amino acid transporters and across the basolateral membrane through an amino acid transporter and/or the organic anion transporter (OATl). These examples provide strong evidence that the nephrotoxicity of numerous xenobiotics is dependent on GSH conjugation-mediated delivery to the kidney. 

OK cells, but not LLC-PKl, cells exhibit basolateral to apical unidirectional transport of p-aminohippurate (PAH) by the organic anion transport system [149]. Moreover, PAH uptake by OK cells from the basalola-teral side was competitively inhibited by the beta-... 

OTA is thought to be transported into the proximal tubular epithelium via organic anion transporters. In primary rabbit proximal tubule cells cultured on microporus supports OTA was taken up from the basolateral compartment and secreted into the apical compartment. This process was sensitive to probenecid [198]. Mouse proximal tubular cells transfected with hOATs (1, 3 and 4) exhibited an enhanced uptake of OTA which was also inhibited by probenecid [199, 200]. However, it is also known that OTA has a high affinity for albumin and it has been demonstrated experimentally that human serum albumin dose depend-ently decreases OTA uptake via hOATl [201]. Whether albumin bound OTA can be transported via megalin mediated endocytosis has not been investigated. 

S. R., Benke, D., Meier, P.J., and Reme, C.E. (2002) Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium. Investigative Ophthalmology eJ Visual Science, 43, 510-514. 

Uchino et al. [84] cloned and characterized an apical PAH transporter isolated from human kidney, named NPTl. NPTl was first identified as a low affinity sodium-dependent phosphate transporter, later it was characterized as an organic anion transporter. In human embryonic kidney cells transfected with NPTl, PAH, urate, benzyl penicillin, faropenem, estradiol-P-glucuronide are transported, and PAH uptake can be inhibited by various organic anions. NPTl does not function as an organic anion exchanger, and thus is... 

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