NDLI: Functional and Pharmacological Comparison of Human, Mouse, and Rat Organic Cation Transporter 1 toward Drug and Pesticide Interaction

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Functional and Pharmacological Comparison of Human, Mouse, and Rat Organic Cation Transporter 1 toward Drug and Pesticide Interaction

Content Provider	MDPI
Author	Floerl, Saskia Kuehne, Annett Hagos, Yohannes
Copyright Year	2020
Description	Extrapolation from animal to human data is not always possible, because several essential factors, such as expression level, localization, as well as the substrate selectivity and affinity of relevant transport proteins, can differ between species. In this study, we examined the interactions of drugs and pesticides with the clinically relevant organic cation transporter hOCT1 (SLC22A1) in comparison to the orthologous transporters from mouse and rat. We determined Km-values (73 ± 7, 36 ± 13, and 57 ± 5 µM) of human, mouse and rat OCT1 for the commonly used substrate 1-methyl-4-phenylpyridinium (MPP) and IC50-values of decynium22 (12.1 ± 0.8, 5.3 ± 0.4, and 10.5 ± 0.4 µM). For the first time, we demonstrated the interaction of the cationic fungicides imazalil, azoxystrobin, prochloraz, and propamocarb with human and rodent OCT1. Drugs such as ketoconazole, clonidine, and verapamil showed substantial inhibitory potential to human, mouse, and rat OCT1 activity. A correlation analysis of hOCT1 versus mouse and rat orthologs revealed a strong functional correlation between the three species. In conclusion, this approach shows that transporter interaction data are in many cases transferable between rodents and humans, but potential species differences for other drugs and pesticides could not be excluded, though it is recommendable to perform functional comparisons of human and rodent transporters for new molecular entities.
Starting Page	6871
e-ISSN	14220067
DOI	10.3390/ijms21186871
Journal	International Journal of Molecular Sciences
Issue Number	18
Volume Number	21
Language	English
Publisher	MDPI
Publisher Date	2020-09-19
Access Restriction	Open
Subject Keyword	International Journal of Molecular Sciences Toxicology Solute Carrier (slc) Family Oct1 Slc22a1 Species Differences Drugs Pesticides
Content Type	Text
Resource Type	Article

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