Organic cation transport apical transporters

Grundemann D, Babin-Ebell J, Martel F, Ording N, Schmidt A, Schomig E (1997) Primary structure and functional expression of the apical organic cation transporter from kidney epithelial LLC-PK1 cells. J Biol Chem 272, 10408-10413. 

The family of organic cation transporters is represented at the apical membrane of intestinal cells by OCTN2, whereas the basolateral membrane is equipped with... 

Many studies have been performed to characterize the requirements for a substrate to be transported by the "organic cation transport mechanism" [97-100]. As for organic anions, the molecular structure of substrates is rather unspecific. Hydrophobicity and basicity are the general characteristics of substrates, but their ionization is not a prerequisite for interacting with the basolateral carrier [65]. Similar properties were found in brush border membrane [97-100]. Although the ratio of basolateral to apical membrane affinities may vary with substrates and animal species [97]. 

Molecular identification of putative apical organic cation transporters... 

ABC, ATP-binding cassette transporter superfamily ASBT, apical sodium-dependent bile salt transporter BCRP, breast cancer resistance protein BSEP, bile salt export pump MDRl, multidrug resistance MRR multidrug resistance-related protein NTCP, sodium taurocholate cotransporting polypeptide OAT, organic anion transporter OCT, organic cation transporter SLC, solute-linked carrier transporter family SLCO, solute-linked carrier organic anion transporter family. 

Y. Kato, M. Sugiura, T. Sugiura, T. Wakayama, Y. Kubo, D. Kobayashi, Y. Sai, I. Tamai, S. Iseki, and A. Tsuji. Organic cation/camitine transporter octn2 (slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse. Mol Pharmacol 70 829-837 (2006). 

The Calu-3 human submucosal gland cell line forms polarized cell monolayers with tight junctions, produces mucus, and develops apical cilia when grown at an air interface. Transport studies can be performed after 10-14 days in culture, and it has been shown that Calu-3 cells express P-gp and actively transport amino acids, nucleosides, and dipeptide analogs organic anions, organic cations, polyamines, and efflux pump substrates are not actively transported.43,51,53-56 Because Calu-3 cells are not subject to the influence of multiple in vivo cell types, the expression of carrier proteins and enzymes may not reflect in vivo levels. Nevertheless, values obtained in Calu-3 permeability studies correlate well with those obtained from primary cultured rabbit tracheal epithelial cells and in vivo rat lung absorption studies.54 Mannitol permeation in Calu-3 cells is about 10 times less than that in vivo, but this is the same ratio difference between Caco-2 cells and in vivo intestinal epithelium.51... 

For example, some SLC on the sinusoidal (basolateral) membrane of hepatocytes take up organic anions, while the ABC on the apical membranes of bile canicular cells excrete them. The combined activities of these two transporters thus results in the vectorial transport of drugs from the blood to the bile. Similarly, the basolateral transporters of the kidney tubular cells act in a coordinated, vectorial manner with apical transporters to secrete organic cations (OCs) from the blood to the urine. 

A few transport mechanisms have been identified in the kidney by expression cloning, which might be involved in the apical step of organic cation secretion, although their function in situ has not been estabhshed. 

Transport of organic cations from cell to tubular lumen across the apical membrane occurs via an electroneutral proton—organic cation exchange mechanism. Transporters on the apical... 

OCTNl (SLC22A4) is expressed in the kidney, trachea, and bone marrow and operates as an organic cation-proton exchanger OCTNl likely functions as a bidirectional pH- and ATP-dependent transporter at the apical membrane in renal tubular epithelial cells. 

---