PortaCellTec biosciences GmbH

Organic Cation Transporters (OCTs)

The physiological, pharmaceutical and pathological role of organic cation transporters (OCTs) of the SLC22 gene family


General overview

The organic cation transporters (OCTs) of the SLC22 gene family are broad-specificity transporters and are critically involved in the uptake, distribution and elimination of cationic drugs. They also participate in excretion and distribution of endogeneous organic cations such as choline, creatinine and cationic neurotransmitters.
Four OCT subtypes, OCT1, OCT2, OCT3 and OCT6, have been shown to be involved in drug excretion and distribution. OCTs exhibit overlapping sites of expression in many tissues such as small intestine, liver, kidney, heart, skeletal muscle, placenta, lung, brain, cells of the immune system, and tumors. In epithelial cells OCTs may be located in the basolateral or luminal membranes.
Transcellular cation movement in small intestine, kidney and liver is mediated by the combined action of electrogenic OCT-type uptake systems and efflux transporters that operate as cation/proton antiporters. Recent data has shown that OCT-type transporters participate in the regulation of extracellular concentrations of neurotransmitters in brain, mediate the release of acetylcholine in non-neuronal cholinergic reactions, and are critically involved in the regulation of histamine release from basophils.
The identification of polymorphisms in human OCTs allows the identification of patients with an increased risk for adverse drug reactions. Recently it has been shown that polymorphisms of OCTs in patients resulted in altered pharmacokinetics and response to drugs such as the antidiabetic drug metformin and the cytostatic drug cisplatin.

Driving force and mechanism of drug transport by OCTs OCT-Schema
OCTs mediate translocation of organic cations
(OC+) in both directions across the plasma membrane. Since they translocate positive electrical charge, cation transport by OCTs is driven not only by the difference in substrate concentration across the plasma membrane but also by the membrane potential. Thus transport of drugs into cells is favoured at normal (inside negative) membrane potential.
The structure of the substrate binding cavities of individual OCT subtypes allows translocation of various drugs with overlapping specificity. If drugs do not fit into the substrate binding cavity they cannot be transported but may act as competitive inhibitors.

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New validated products:

  • mNtcp
  • mOct1

Events

3rd German Pharm-Tox Summit
Göttingen, Germany
26 February - 1 March 2018


Pharmaforum
Saarbrücken, Germany
8 March 2018

 

AAPS Workshop
Virginia, USA
16 - 18 April 2018

 

20th Barrier- and
Transporter-Meeting

Bad Herrenalb, Germany
7 - 9 May 2018

Greifswalder Transporttage 2018
Greifswald, Germany
October 2018

 


Guidance for Industry (FDA and EMA)

Publications