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OCT3 (SLC22A3)

Molecular structure and Tissue distribution
The tissue expression pattern of OCT3 is very broad. At variance to OCT1 and OCT2, OCT3 is not only expressed in epithelial cells and neurons but also in muscle cells and glial cells. In humans, the strongest expression was found in skeletal muscle, liver, placenta and heart, however, OCT3 was also expressed in many other organs including brain and in some cancer cell lines. In rodents, expression of OCT3 was detected in additional organs and basophile granulocytes. In humans, OCT3 protein has been localized to the basolateral membrane of the trophoblasts in placenta, to the sinusoidal membrane of hepatocytes, and to the basolateral membrane of epithelial cells of renal proximal tubules. At variance, OCT3 protein was localized to luminal membranes of bronchial epithelial cells and small intestinal enterocytes. In brain of rodents, expression of OCT3 was observed in hippocampus, area postrema, subfornical organ, medial hypothalamus, and ependym of the third ventricle.

Interaction of OCT3 with endogenous compounds and drugs.
Translocation of MPP by hOCT3 exhibits similar Km values as hOCT1 and hOCT2,
whereas a much higher Km value was measured for hOCT3-mediated transport of TEA. A much lower affinity for the inhibition of hOCT3 compared to hOCT1 and hOCT2 was observed for amantadine, memantine, phenylcyclidine, clonidine, diphenyl­hydramine, atropine, procainamide and cocaine. Among the substrates of hOCT3 the highest affinities were obtained for MPP (47 µM) and histamine (180-220 µM). High affinity inhibitors of hOCT3 are disprocynium 24 (IC50 value 0.015 µM), decynium 22 (IC50 value 0.1 µM), and corticosterone (IC50 value 0.12-0.29 µM).
Example for biomedical impact: Changes of OCT3 acitivity are correlated with changes of brain function.

Figure 1 Concentration dependent OCT3 mediated MPP uptake Figure 2 Inhibition of OCT3 mediated MPP uptake by decynium22

 

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New validated products:

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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
7 - 9 September 2018

 


Guidance for Industry (FDA and EMA)

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