Primacyt Transporter Assays - ADME - Toxicology Assays

OATPs - Organic Anion transporting Polypeptides

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Primacyt is a functional precision service organization in the field of OATPs. We offer a broad portfolio of transporter assays for OATPs. We support industry, research organizations and government in the field 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.

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

  • OATP assays, inhibition assays, transporters, inhibitors, OATP in vitro, transport proteins or hepatic uptake transporters and more.

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

OATPs in 30 seconds.
OATPs are organic anion transporting polypeptides and form a superfamily of transporters.

Transporters are membrane transport proteins primarily for the moderation of the transport of organic anions across the membranes of cells. OATPs play the role of a cell gatekeeper. As solute carrier family (SLC) members, they are located in the lipid bilayer of the membrane. OATPs are expressed in the liver. In different tissues they appear on basolateral and apical membranes, transporting anions and as neutral and cationic compounds. The eleven human OATPs split into 6 families plus ten subfamilies according to their identity of amino acids.

OATPs mediate sodium-independent the transport of a broad range of endo- and xenobiotics. Although most substrates are amphipathic organic anions with a molecular weight of more than 300 Da, some of the OATPs are transporters for neutral or positively charged substrates. Known substrates are, e.g., statins, bile salts, triiodothyronine (T3), thyroxine (T4), prostaglandins, antibiotics, anticancer agents and cardiac glycosides. Eleven OATPs are known in humans expressed in a variety of different human tissues including brain, intestine, liver and kidney and are involved in drug absorption, distribution, and excretion. Because of the broad tissue expression and broad substrate spectrum, OATPs can be determinates for alteration of drug kinetics.

Moreover, known genetic variants of OATPs are known to influence the transporter-mediated uptake of drugs resulting in a reduced or increased drug bioavailability with possible severe side effects and/or drug-drug interaction (DDI).

OATPs have significant regulatory importance. OATP1B1 and OATP1B3 are explicitly named as clinically relevant transporters by the FDA (Federal Drug Administration and EMA (European Medicines Agency). OATP1B1 and OATP1B3 substrate potential should be assessed clearance of the compounds.
OATP Uptakes
OATPs mediate the sodium-independent uptake of a wide range of amphiphilic substrates, including many drugs and toxins.

It should be clear that the importance of organic anion transporting polypeptide OATP1B1and 1B3 in the clinical pharmacokinetics of substrate drugs is evident.

When drugs get eliminated from the body by extensive metabolism, the hepatic uptake is a key determining process of the intrinsic hepatic clearance of OATP substrates.

A broad substrate specificity characterizes OATPs. OATP1B1 or OATP1B3 are in a position to alter organic anions. Several kinds of events, such as drug-drug interactions (DDI) or genetic polymorphisms of transporter genes, can modify the hepatic clearance of many kinds of structurally-unrelated drugs.

These alterations of pharmacokinetics may lead to modified pharmacological effects and adverse reactions, for example, statin-induced myotoxicity and the glucose-lowering effect of anti-diabetes drugs.
Pharmacogical Relevance
Many drug-drug interactions have been correlated with OATPs, negatively impacting the pharmacokinetics and pharmacodynamics of drugs.

The most critical issue is the inhibition of the transport of a second drug into the hepatocyte, so that it is retained longer in the body, increasing the plasma half-life. The most relevant payers for interactions are OATP1B1, OATP1B3 and OATP2B1. They are present at the hepatocyte basolateral (sinusoidal) membrane.

OATP1B1 and OATP1B3 are known to play an essential role in hepatic drug disposition.

These OATPs contribute towards the first step of hepatic accumulation and can influence the disposition of drug via the hepatic route. The most clinically relevant interactions can be associated with the lipid-lowering drugs statins.

SNPs - single nucleotide polymorphisms - are also associated with the OATPs, primarily OAT1PB1, and may have a significant influence on the transporter activity
Inhibition Assays
Inhibitory properties of drug acting activities (DAA) related to organic anion transporting polypeptides functions of OATPB1 and OATPB3 are known. For future analysis and validation of compounds, the pharmacokinetics of new and repositioned drugs must be assessed, preferentially related to the uptake of human hepatocytes. We have to ensure that there is no inhibition of inhibiting OATPs to avoid potential risks of drug-drug interaction.

Important questions arise from the potential inhibitory characteristics of OATPB1 and OATB3. Your organization and Primacyt need to define possible cross relationships potentially caused by the combination of different substances and concentrations. The resulting profiles serve to eliminate DAA mediated inhibitions during therapy.
Hepatic Uptake Transporters
The liver is of primary importance for all aspects in drug disposition, mainly in distribution, absorption, metabolism, and excretion.

Responsible for the elimination and clearance of drugs through the biliary system or the enterohepatic recirculation, hepatic uptake / efflux-transporters gain significance. Prior models are based on the assumption that metabolism driven enzymes like cytochromes P450 and CYPs inhibit or induce DDIs. Now it comes to higher attention that higher uptake, metabolism or efflux may be impaired or promoted by the interaction of the other drug or drugs with the same pathway or metabolism enzyme.

The absorption of drugs into the liver from the hepatic artery of the portal vein. The A series of uptake transporters on the plasma membrane of the liver. OATP transporters are classified as relevant for specific drug-drug interactions.

Notable from the groups of OATPs are OATP1B1, 1B3, and 2B1 as well as OCT1, an organic cation transporters and, OAT2 and OAT7 organic anion transporters, and the sodium taurocholate co-transporting polypeptide NTCP.

Examples of drug-drug interactions are statins, known as a substrate for OATP1B1 as prescribed for lowering the level of cholesterols and Simvastatin. Uptake of Simvastatin to the liver can get impaired by drug-drug interactions, reducing the function of OATP1B1, or, as a result in increased drug-specific higher plasma concentrations and enhanced risk of myopathy, induced by Simvastatin, an enhanced risk of simvastatin-induced myopathy.
Overview about selected Primacyt OATP 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:

Transporters and Tissue Expression
Liver, brain, kidney, small intestine, lung, heart
Brain, Kidney, liver, small intestine

Fluorescein methotrexate (FMTX)
Rhodamine 123
Taurocholic acid

Kupffer Cells (KC) are specialized macrophages located in the liver. They line the walls of the sinusoids, and residing within the lumen, and form a part of the mononuclear phagocyte system. An alternate term for Kupffer Cells is stellate macrophages or Kupffer-Browicz cells.

Kupffer cells represent about 80-90 percent of the tissue macrophages in the body. Kupffer cells are permanently exposed to gut-derived bacteria, bacterial endotoxins, and microbial debris.

Kupffer cells in the liver catch and destroy old, worn out red blood cells, transferring their components to hepatocytes. To a certain extent, Kupffer cells partially degrade bacterial antigens before handing them on to the hepatocytes for excretion into the bile.

They handle LDL lipoproteins whereas the HDL proceeds directly into the hepatocytes. They are capable of producing mediators like interleukin-1 (IL1), interleukin-6 (IL6) and Tumor Necrosis Factor α (TNFα), moderating protein synthesis by the hepatocytes. On a regular basis, they produce prostaglandins, which are cytoprotective for hepatocytes.

Although their primary function is phagocytosis and defense of the liver against bacteria, endotoxaemia, and viral infections, they also fulfill other vital roles. They partially degrade bacterial antigens before handing them on to the hepatocytes for excretion into the bile. They handle LDL lipoproteins, whilst the HDL proceed directly into the hepatocytes. They produce lymphokine mediators that direct protein synthesis by the hepatocytes. Also, they usually produce prostaglandins that are cytoprotective for the hepatocytes.

When Kupffer cells attack infected hepatocytes or cancer cells, then they begin to produce leukotrienes.
A Biological Membrane is a membrane for enclosing or separating purposes. Such a membrane is a selective barrier within living objects with permeable characteristics.

Biomembranes consist of lipids, proteins, and carbohydrates. The latter is attached either as lipid forming glycolipids of various classes or as proteins forming glycoproteins. Lipids in a cell membrane provide a fluid matrix for proteins to rotate and laterally diffuse for physiological functioning.

Biological Membranes are containing an identical basic structure, composed of molecules called Phospholipids, which form a Phospholipid Bilayer. A phospholipid is a lipid made of glycerol, two fatty acid tails, and a phosphate-linked head group.

Biological membranes have three primary functions:

  • Housekeeping, removing toxic substances out of the cell;
  • Housing receptors and channels that allow specific molecules to pass between organelles and between the cell and the outside environment. These activities refer to ions, nutrients, wastes, and metabolic products for the mediation of cellular and extracellular activities.
  • Control of the movement of substances in and out of cells and organelles and Separation of vital but incompatible metabolic processes conducted within organelles.
The term Active Transport describe the processes of moving materials through the cell membrane that requires the use of energy. Active Transport can be characterized by

  • the Sodium-Potassium pump for the maintainance of the membrane potential. Three Na+ ions out of the cell for every two K+ ions are moved into the cell
  • by Exocytosis, and
  • by Endocytosis.

In contrast, a secondary active transport is an indirect transport, involves the coupling of the molecule with another mnolecule moving along an electrochemical gradient from regions of high concentration to regions of low concentration. No energy is used in this process, because molecules moving freely along such processes as osmosis or diffusion.

Osmosiscan be described as a net movement of water across a selectively permeable membrane. It is driven by a difference in solute concentrations on the two membrane sides. A selectively permeable membrane is one that allows unrestricted passage of water, but not solute molecules or ions.
Simple diffusion is occurring without the aid of a carrier molecule driven by the force of diffusion. Such particles or substances move from higher to lower concentration.

Molecules can pass through the cell membrane by simple diffusion belong to the groups of carbon dioxide, oxygen, and ethanol.

Facilitated diffusion is an assisted diffusion requiring a carrier molecule. Alternate terms to facilitated diffusion are facilitated transport or passive-mediated transport, described as the process of spontaneous of molecules or ions across a biological membrane via specific transmembrane integral proteins.
A transporter is a membrane transport protein. It is involved in the movement of ions, small molecules, or macromolecules across a biological membrane.
The lipid bilayer or phospholipid bilayer, as the term is telling, is a thin polar membrane made of two layers of lipid molecules. Such membranes are flat constructs for the formation of a continuous barrier around all cells.

The proteins and lipid molecules are held together by noncovalent interactions. It is based upon the Van der Waals forces for holding the hydrophobic tails. Another principle is hydrogen bonding. Such bonding mechanism binds the hydrophilic heads with water.
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Thank you for your interest in Primacyt assays. Please open the project Inquiry form to contact us.

We keep your data strictly confidential. PRIMACYT respects your and your company's privacy.

I have read the Privacy Policy note. I agree that my details and data will be collected and stored electronically to answer my request. Note: You can revoke your consent at any time in the future by e-mail to the e-mail address