Physiological and Pathophysiological Regulation of Transporters for Organic Cations

  • Eberhard SchlatterEmail author


Transporters for organic cations (OCTs, OCTNs, MATEs) are polyspecific membrane proteins which translocate many organic and some inorganic cations across plasma membranes in a driving force dependent and saturable manner. These transporters are responsible for the cellular uptake and extrusion of many cationic drugs and toxins and therefore prerequisite for their metabolism, therapeutical actions, but also for their negative side effects. Together with the molecular identification of these transporters data were published from in vivo and in vitro experiments demonstrating that drug transport is regulated independent of changes in their driving forces. In this chapter the manyfold regulation of OCTs, OCTNs, and MATEs from various mammals including humans is summarized. These regulatory processes involve both changes in substrate affinities (Km) as well as in transport capacity (Vmax) or changes in expression rates. Importantly, all these regulatory processes of the various transporter proteins are highly paralog and ortholog dependent. Acute effects of various protein kinases on transport activity within minutes has been demonstrated, including effects on the transporter molecule itself as well as on transporter trafficking to and from the membrane. Kinases and several other cytosolic factors are involved in a chronic regulation of the expression of transporters for organic cations in several organs. In addition, transporter expression is also epigenetically regulated, a mechanism which apparently contributes to the organ specific expression of the transporters. It also plays a role in altered transporter expression in tumor tissues, a feature which is highly relevant for drug efficiencies in antitumor therapies. Finally, in this chapter many studies on transporter regulation in very divers pathophysiological situations including several hepatic or renal diseases are discussed


Transport regulation Protein kinases Transcriptional regulation Translational regulation Epigenetic regulation Substrate affinity Protein trafficking Pathophysiological regulation Cytosolic factors Nuclear factors 


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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Experimental Nephrology, Medical Clinic DUniversity of MünsterMünsterGermany

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