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Primacyt Transporter Assays - ADME - Toxicology Assays


OCT - Organic Cation Transporters


Start your Project and why you should contact us.

Primacyt is a functional precision service organization in the field of OCTs. We offer a broad portfolio of transporter assays for OCTs. We support industry, research organizations and government in the area of in vitro studies related to drug interaction from the beginning of your projects until preclinical completion.


We are highly committed to offering additional categories of laboratory services and analytical topics as a commitment to the continuous expansion of our leading position in the industry. We are your partner and the partner of your clients in the education, training, and development of testing protocols. We also offer permanent routine lab services as a customized approach and service. You are in a position to open up additional revenue streams for your organization and partners.

Primacyt is your partner for Uptake Transporter Studies.

We support your projects with assays on demand. Our cell platform uses stable transfected HEK293 cells expressing human OCTs. Optionally, we are offering other cell lines and cells from your sources. Suitable substrates and inhibitors are according to your requirements.

Our assay contribution comprises inhibition assessments and substrate assessment. Bases on your portfolio requirements, we are glad to extend your portfolio with additional analytical steps.
Concerning drug-drug interaction studies, our inhibition assays use uptake transporter substrates according to your needs. Substrate assays can be based on perpetrator
compounds. Our assay setup targets the testing the drug-drug interaction of the test compound with any potential perpetrator compound.


Our partners contact us for getting advice on many questions and facts related to


  • OCT1, OCT2, OCT3
  • Organic Cation Transporters
  • OTC Organic Transporter Assays and more

We are your partner when it comes to questions about drug-drug interaction or related lab service work for drug development.

OCTs in 30 seconds.

Organic cation transporters OCTs are uptake transporters and members of the solute carrier (SLC) gene family SLC22A. They are expressed in several epithelial membranes in different organs of the body (e.g., liver, intestine, kidney, heart, brain, and placenta).


OCTs consist of twelve transmembrane domains and mediate the passive facilitated diffusion of several organic cations alongside their electrochemical gradients. Substrates are structurally unrelated small organic cations, including endogenous and exogenous substrates and many drugs (e.g., creatinine, dopamine, progesterone, anesthetic drugs like ketamine, anticancer drugs like cisplatin and many more.

Although the OCT-mediated transport is independent of the pH value, affinity for several substrates like ketamine does depend on their degree of ionization, leading to an increased transport rate of those substrates at reduced pH values. Genetic variants of OCTs might result in a change of bioavailability of drugs leading to possible severe side effects and drug-drug interaction (DDI).

Organic cation transporter (OCTs) are primarily responsible across the cell membrane for the transport of serotonin and the catecholamines. Catecholamines comprise the hormones produced by the adrenal glands, localized on top of the kidneys. The central catecholamines are dopamine, epinephrine, and norepinephrine.

Organic cation transporters OCT1 and OCT2 are recognized as highly clinically relevant and play an essential role in drug-drug interactions DDIs.

Differentiation of Subtypes OTC1, OTC2, OTC3

Organic Cation Transporter 1 – OCT1
OCT1 is predominantly regarded as a hepatic uptake transporter. Expressed on the sinusoidal membrane of hepatocytes at the blood side. They play an essential role in the disposition and response as well as for the hepatic clearance of mostly cationic drugs and endogenous compounds.

Organic Cation Transporter 2 – OCT2
OCT2 is a polyspecific renal uptake transporter, expressed on the basolateral blood side of proximal tubule cells. It plays a crucial role in the disposition and renal clearance of mostly cationic drugs and endogenous compounds.

Organic Cation Transporter 3 – OCT3
OCT3 is a polyspecific uptake transporter with ubiquitous tissue distribution, expressed in the liver and the kidney. Relative to OTC1 and OTC2, OTC3 plays a lower role in liver and kidney respectively. Its tissue distribution indicates its importance for drug tissue distribution. Also, it seems to have some significance in cardiac tissue drug exposure.

OCT3 is regarded as significant in oral absorption, acetylcholine release during extraneuronal cholinergic regulations, as well as regulation of histamine release from basophils. OCT3 is vital in the context of neurotransmitter re-uptake in the brain. There is still uncertainty if whether its location is primarily neuronal or glial. Brain regions include the hippocampus, Cortex (visual and retrosplenial), the hypothalamus, amygdala, nucleus accumbens, thalamus, raphe nucleus, subiculum, superior and inferior colliculi, as well as islands of Calleja.

Project Schedule - How we can work together
Primacyt Cell Culture GmbH provides cell culture solutions for biomedical and cell biology research. PRIMACYT is focused on in-vitro-technologies, certified according to GLP. Our focus is in the fields of hepatocytes, subcellular fractions, skin tissues, cell culture media, 2D and 3D cultures, collagen products, and SILAC media solutions. We provide solutions for human and animal research.

According to the needs of your organization, we can agree on a mutual confidentiality agreement. We discuss your project needs and send you the first offer with the contractually relevant project details.

Our past cooperation partners foresee different needs for the formal contracts the parties need to agree upon. As typically our joint projects are relatively uncomplicated relative to drug discovery projects, we suggest a simple, fast-track approach to save your time for the benefit of your projects.

We are in a position to provide umbrella type contract versions, followed by a project amendment or package everything in a single document. We are prepared to send you templates for such agreements including material transfer agreements when needed. Contract languages can be English or German for you as a commercial or government / academic entity.

We always suggest to exchange data through cloud mechanisms and to cooperate by life video or telephone conferences also in other languages including Chinese.



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Localization of Organic Cation Transporters
OCT1

OCT1 is primarily expressed on the blood sided sinusoidal membrane of hepatocytes. Besides, OCT1 is situated on the basolateral membrane of small intestinal enterocytes and renal proximal tubular cells. To a lower extent, OTCs can be found some neurons, in the heart, skeletal muscle, lung, tumor cells, and basophilic granulocytes.


OCT2

OCT2 is mostly expressed on the blood side of the basolateral membrane of renal proximal tubule cells. It is not represented in the liver but can be found in some other tissues at lower levels, e.g., small intestines, trachea and bronchi, skin, placenta, brain, and the choroid plexus.

OCT3

OCT3 has a comprehensive tissue-specific expression pattern. OCT3 is expressed in neurons, glial cells, and epithelial cells of the choroid plexus. In humans, they can be identified in the kidney, liver, placenta, heart, and skeletal muscles. To a lower extent, OTC3 can be found in the lung, brain, and in cancer-derived cell lines.

OCT3 is localized at the basolateral membrane of trophoblasts in the placenta, the sinusoidal membrane of hepatocytes, the basolateral membrane of renal proximal tubule epithelial cells, as well as the on luminal membranes of bronchial epithelial cells and small intestinal enterocytes [1, 7].

OCT3 is localized at the basolateral (blood-facing) and apical (saliva-facing) membranes of salivary gland acinar cells. This confirms a dual role of the PCT2 transporter in mediating the uptake and efflux of organic cations in the salivary glands.
OCTs and MATEs
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OTCs and MATEs

OCT1


OCT1 is the crucial step in the active hepatic extraction of cationic drugs. Since the discovery of MATEs, DDIs allocated to OCTs get reevaluated. OTC1 cooperates with the facilitating MATE1 improving the biliary elimination of OCT1 substrates transported into the liver. It is essential to know, that the liver-specific OCT1 shares many substrates and inhibitors with the kidney-specific OCT2 and OCT3 and OCTNs.

MATE1 in the liver provides the final step in the elimination of drugs from the hepatocyte into the bile. This is complementing the OCT1 uptake from the blood. When primarily renal, OCT2 represents a second systemic clearance mechanism.

Overall OCT1 is evaluated as number one step in progressive hepatic elimination, then followed by MATEs as number two.

OCT2

OCT2 cooperates with MATE1 and MATE2-K which facilitate the elimination of OCT2 substrates into the urine.

Since the discovery of MATEs, DDIs attributed to OCT2 are reexamined, potentially resulting in new priorities for MATEs. Regardless, OCT2 has the highest level of importance in the active renal secretion of cationic drugs.

OCT2 shows an important cross-specificity with OCT1 and OCT3 related to a variety of substrates and inhibitors, also including OCTNs and members of the MATE transporter family of transporters. MATE1 and MATE2-K in the kidney constitute the final step in the elimination of drugs from the proximal tubule cells into the lumen (urine). This is complementing the OCT2 uptake from the blood.

The role of OCT2 as the first step in active renal secretion is dominating also in the case, when DDIs may be attributed to MATEs.

OCT3

OCT3 is a transporter for a wide range of monoamine neurotransmitters, hormones, and steroids. Its broad substrate profile is overlapping with OCT1, OCT2, and MATE1 / MATE2-K. Expressed in kidney and the liver, OCT1 and OCT2 are evaluated as superior to the MATEs at their respective locations.

Literature
Literature


Jouan E et al. The mitochondrial fluorescent dye rhodamine 123 is a high-affinity substrate for organic
cation transporters (OCTs) 1 and 2. Fundam Clin Pharmacol. 2014, 1: 65-77

Bachmakov I et al. Interaction of oral antidiabetic drugs with hepatic uptake transporters: focus on organic
anion transporting polypeptides and organic cation transporter 1. Diabetes. 2008, 57:1463-1469

Wu X et al. Structure, function, and regional distribution of the organic cation transporter OCT3 in the
kidney. Am J Physiol Renal Physiol. 2000, 279:F449-F458

Overview of Primacyt Assays
Primacyt is using stable transfected HEK293 cells as basis for our assays. We analyze the uptake functions using suitable substrates, inhibiting the uptake by adding the reference inhibitors.

Prímacyt offers assays comprising the following possible options:

Transporter and Tissue Expression
OCT1 – Liver, kidney, intestine
OCT2 – Kidney, lung, neurons
OCT3 – Liver, brain, placenta, kidney, intestine, heart, lung

Substrates
Rhodamine
MPP+ (1-Methyl-4-Phenyl-Pyridinium)

Inhibitors
Quinidine
Verapamil
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You have reached this page because you might be interested in the following topic areas:
step in cation reabsorption, twelve putative transmembrane domains, in a wide array of drugs, focus on endogenous small organic cations,
or a plasma integral membrane protein. The following terms might be important for you: cation transporter 1 oct1, combination of oct1 and oct2, human organic cation transporters, transporter genes, drugs and environmental toxins as well as multidrug and toxin extrusion, and finally similar cation transporter genes. Please use the project inquiry form to ask for any topic of specific interst for your discovwery projects.