Mammalian kidney and liver are critical in maintaining physiological ionic environment. Kidney specializes in removing toxins, drugs, and other organic anions from the blood to extracellular space across the tubular epithelium into the lumen of nephrons by a process called "renal secretion". Organic solutes must enter the cell via the basolateral membrane, move inside the cells, and then transported into the lumen across the apical membrane. Therefore, specialized proteins or transporters must reside at the basolateral and apical membranes that can transport various organic solutes against the gradient (active transport). The major, known renal secretory transport systems are multispecific and have been placed into two distinct groups: the organic anion transporter (OAT) and organic cation transporter (OCT). The classic substrate for OAT are p-aminohippurate (PAH), phenol red, and methotrexate, whereas tetraethylammonium (TEA) and N-methylnicotinamide (NMN) have been used to study OCT. The renal secretion system has major clinical importance regarding pharmacokinetics of anionic drugs such as diuretics and penicillins. Besides kidney, anionic substrates are also transported in other organs, e.g., choroid plexus, eye, airway, and placenta. Therefore, OAT may have wide physiological implications in anion transport.

Recently, several multispecific organic anion transporters 1-3 have been cloned and characterized from kidney, liver and other tissues (OAT1-3, OAT-K1 and OATK2). OAT family of proteins has 12 transmembrane domains with cytoplasmic N and C-terminus. Rat Kidney PAH transporter, termed OAT1 or ROAT1, encodes a protein of 551 aa. Human OAT1 (hOAT1) is 563 aa and its alternatively spliced isoform hOAT2 is 550 aa (missing 13 aa from 523-533 aa). OAT1 has wide substrate selectivity, covering endogenous substrates such as cyclic nucleotides, prostaglandin and uric acid, and a variety of drugs (e.g., antibiotics, non-steroidal anti-inflammatory drugs, diuretics, anti-neoplastic drug, and a uricosuric drug). OAT1 has been localized on the basolateral membrane of the proximal tubule in the kidney. Weak expression was also detected in brain. OAT1 has ~95 identity with mouse kidney NKT, an ortholog of rat OAT1. OAT2, previously called NLT (novel liver-specific transporter) shows 42% homology with OAT1. OAT2 (rat 535 aa; human 548 aa) is predominantly expressed in liver, and to a lower level in kidney. OAT2 mediates sodium-independent, multispecific organic anion transport (PAH, salicylate and acetylsalicylate, prostaglandin E2, and dicarboxylate).

Recently OAT3 (rat 536-aa, human 568 aa) has been cloned that is most closely related to OAT1 (~49% identity). Rat OAT3 is expressed in the liver, brain, kidney and eye. OAT3 also mediates Na-independent uptake of several organic anions (PAH, ochratoxin, and estrone sulfate, etc). OAT3 shows 92% homology with mouse Roct (reduced in osteosclerosis transporter), possibly an ortholog of rat OAT3. As compared to OAT1-2, strong expression of OAT3 in brain suggests its role in removing organic anion in the brain.

A kidney-specific anion transporter termed OAT-K1 (rat 669 aa) has been cloned from rat kidney. OAT-K1 mRNA is specifically expressed in brush-borer membrane of the proximal straight tubules. Rat OAT-K1 (669 aa) shows 72% identity with rat liver oatp. It mediates basolateral uptake of anionic methotrexate but not PAH, taurocholate, and prostaglandin E2. OAT-K2 (498 aa), very similar to OAT-K1 (91% identity), has also been cloned from rat kidney. It also has 62-65% homology with oatp1-3 family of proteins. OAT-K2 is predominantly expressed in convoluted tubules, proximal straight tubules, and cortical collecting ducts. OAT-K2 mediates uptake of hydrophobic anions such as taurocholate, methotrexate, folate, and prostaglandin E2 suggesting that OAT-K2 participate in epithelial transport of hydrophobic anionic compound in the kidney.

ADI has produced highly specific rabbit antibodies for OAT1-3, OAT-K1, and OAT-K2 using antigenic peptide sequences unique to each protein. These antibodies do not crossreact with each other and can be used to study various transporters. Respective antigenic or control peptides are also available to confirm specificity of antibodies.
 

m=mouse; r=rat; h=human; ch=chicken; f=frog; ~CT or ~NT=near C or N-terminus. EC=Extracellular; CP=Cytoplasmic domain;


"Neat Antisera" are the unpurified antiserum and it is suitable for ELISA and Western.
"Affinity pure" IgG may be more suitable for immunohistochemical applications and to reduce background in most immunological applications.
"Control peptides" can not be used for Western as they are very short peptides. They are intended for ELISA or antibody blocking studies to establish antibody specificity.

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