Organic Cation Transporter 1 OCT1 Not Vital for Life but of Substantial Biomedical Relevance

ORGANIC. CATION. TRANSPORTER. 1. (OCT1):. NOT. VITAL. FOR. LIFE,. BUT. OF. SUBSTANTIAL. BIOMEDICAL. RELEVANCE. Topic Editors: Jurgen Brockmoller, University Medical Center Göttingen, Germany Mladen Vassilev Tzvetkov, University of ...

Author: Jurgen Brockmoller

Publisher: Frontiers Media SA

ISBN: 9782889740291

Category: Science

Page: 145

View: 831


Around one third of all biologically relevant small molecules are organic cations. These include endogenous substances like catecholamines and other neurotransmitters, toxins and drugs designed to affect signaling processes. The organic cation transporter 1 (OCT1) is among the strongest expressed membrane transporters at the sinusoidal (blood-facing) side of liver cells and contributes substantially to the clearance of the blood from numerous organic cations. A most striking feature of OCT1 is its pronounced genetic diversity. Between 1 and 10% of all human populations have little to no OCT1 activity. With several of the OCT1 substrates up to 10% of Europeans are functionally OCT1 deficient. Apparently, the lack of OCT1 do not lead to apparent substantial pathological changes in these individuals. It thus appears that this transporter is not essential to human life, but does it means that OCT1 is irrelevant? In the last 25 years since the first cloning of this transporter, data on its pharmacological and physiological relevance is steadily accumulating. Numerous clinically relevant drugs (e.g. metformin, morphine, fenoterol, sumatriptan, tramadol and tropisetron) have been shown to be substrates of OCT1, and OCT1 deficiency has been shown to affect the pharmacokinetics, efficacy, or toxicity of these drugs. Also vitamin B1 has been shown to be a substrate of OCT1, and in genetically modified mice OCT1 substantially modulated hepatic lipid metabolism, total body fat and systemic glucose and lipid concentrations. Still, numerous important questions remain unsolved: For which drugs, toxins, or other endogenous or exogenous substances is OCT1 relevant? How can we predict the relevance of OCT1 from in vitro studies? What determines the substrate selectivity of OCT1 in comparison to other transporters or transport processes for organic cations? What regulates the expression of OCT1 in the liver and possibly in other tissues? What is the impact of OCT1 variation in different areas of medicine, including the therapies for cancer as well as for pulmonary, cardiovascular, or neurological diseases? How can evolutionary biology contribute to a better understanding of the roles of OCT1? And, importantly, what types of research are likely to significantly further the knowledge on OCT1 in the next decades?

10 Years of Pharmacogenetics and Pharmacogenomics

... “Organic Cation Transporter 1 (OCT1): Not Vital for Life, but of Substantial Biomedical Relevance”, “Liquid Biopsy as a Tool for Precision Oncology: New Challenges to Assess Clinical Response”, and “Recent Developments in ...

Author: Jose Agundez

Publisher: Frontiers Media SA

ISBN: 9782889638284


Page: 281

View: 941


The Specialty Section “Pharmacogenetics and Pharmacogenomics” makes part of two different Journals: Frontiers in Pharmacology and Frontiers in Genetics. This Specialty Section focuses on the mechanisms by which genetic variations influence drug effects and adverse drug events, and cover basic research, clinical translation, applications in drug development and regulatory issues related to this field. Also, studies addressing the role of other factors such as epigenetics, phenotypic factors or drug-drug interactions on drug pharmacokinetics or pharmacodynamics are welcome. The editorial board is composed of 34 Associate Editors which, together with the Guest Associate Editors and the Reviewer Editors, constitute a team of nearly 340 leading experts in the field of Pharmacogenetics and Pharmacogenomics. This guarantees high quality in the reviewing process as well as short review times. A look back: 10 years of Frontiers in Pharmacogenetics & Pharmacogenomics (Continued in eBook)