Electrolyte Blood Press.  2006 Mar;4(1):8-17. 10.5049/EBP.2006.4.1.8.

Introduction of Organic Anion Transporters (SLC22A) and a Regulatory Mechanism by Caveolins

Affiliations
  • 1Department of Laboratory Animal, Medical Research Center, College of Medicine, Yonsei University, Seoul, Korea.
  • 2Department of Pharmacology and Toxicology, College of Medicine, Inha University, Inchon, Korea. shcha@inha.ac.kr

Abstract

The kidney is an important organ for controlling the volume of body fluids, electrolytic balance and excretion/reabsorption of endogenous and exogenous compounds. Among these renal functions, excretion/reabsorption of endogenous and exogenous substance is very important for the maintenance of physiological homeostasis in the body. Recently discovered organic anion transporters (OAT or SLC22A) have important roles for renal functions. It is well known as drug transporter. Several isoforms belong to SLC22A family. They showed different transport substrate spectrums and different localizations within the kidney. Their gene expressions are changed by some stimulus. The functional transport properties are regulated by protein kinase C. In addition, the function of organic anion transporters are also regulated by protein-protein interaction, such as caveolin which is compositional protein of caveolae structure. In this review, we will give an introduction of organic anion transporters and its regulatory mechanisms.


MeSH Terms

Body Fluids
Caveolae
Caveolins*
Gene Expression
Homeostasis
Humans
Kidney
Multidrug Resistance-Associated Proteins
Organic Anion Transporters*
Protein Isoforms
Protein Kinase C
Xenobiotics
Caveolins
Multidrug Resistance-Associated Proteins
Organic Anion Transporters
Protein Isoforms
Protein Kinase C
Xenobiotics

Figure

  • Fig. 1 Amino acid sequence and membrane topology of rat organic anion transporter 1. OATs show both N-terminus and C-terminus in intracellular site.

  • Fig. 2 Mechanisms of organic anion transport in renal tubular epithelial cells. Transepithelial movement of organic anions across basolateral or apical membrane is mediated by OATs.

  • Fig. 3 The structure of caveolae in plasmamembrane. The small flask shapes indicated by arrow were caveolae (from Vol. 46: H2222, Am J Physiol, 1999). Bar, 120 nm.

  • Fig. 4 Western blot analysis using isolated membrane fraction and immunoprecipitates by antibodies in the rat kidney. A) The kidneys were lysed using a teflon/glass homogenizer and a sonicator, and subjected to sucrose gradient centrifugation as described under Materials and Methods. B) Cell lysates were immuno-precipitated initially with antibodies of rOAT3 or Cav-1 and the respective immuno-precipitated proteins were loaded onto each lane of a 10% SDS-polyacrylamide gel. Kidney lysate was immuno-precipitated initially with rOA3 (left pannel) and was immuno-precipitated initially with Cav-1 antibodies (right pannel).

  • Fig. 5 The effects of Xenopus laevis sense or antisense oligodeoxynucleotide on rOAT3-mediated [3H] estrone sulfate uptake in Xenopus laevis oocyte expression system. Defolliculated stage VI and V oocytes were injected water, rOAT3 cRNA (20 ng/oocyte) with/without senese or antisense ODN (3 or 10 pmol/oocyte).


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