Fluo-cAMP is transported by multidrug resistance-associated protein isoform 4 in rat choroid plexus

Journal of Neurochemistry
Valeska ReichelRosalinde Masereeuw

Abstract

The choroid plexuses (CP) are responsible for transport of micronutrients into brain and clearance of toxic compounds, in addition to its barrier function and production of CSF. Multidrug resistance-associated protein (Mrp) 4 is one transport protein highly expressed in CP tissue and is characterized as a versatile pump for toxicants and signalling molecules. Aim of the study was to determine transport characteristics of a fluorescent cAMP analog in rat CP and to define whether fluo-cAMP can be used for analyses of function, substrate/inhibitor specificity and regulation of Mrp4. Confocal imaging was used to analyze transport mechanisms in absence and presence of various modulators of organic anion transport in freshly isolated and functionally intact CP. Fluo-cAMP transport was saturable, selective, concentrative and metabolism-dependent, following an active two-step mechanism composed of apical uptake into epithelial cells and basolateral efflux. Uptake included a Na(+) -dependent and a Na(+) -independent component and was inhibited by estrone sulfate, taurocholate and sildenafil indicating involvement of organic anion transporting polypeptide Oatp1a5. Efflux was composed of an indirect Na(+) -dependent component and a compon...Continue Reading

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Citations

Jan 5, 2014·The Journal of Pharmacology and Experimental Therapeutics·David S Miller
Mar 8, 2012·Expert Opinion on Drug Metabolism & Toxicology·Péter KrajcsiIstván Sziráki
Jun 9, 2015·Expert Opinion on Drug Metabolism & Toxicology·Olivier FardelYannick Parmentier
Sep 28, 2012·Thrombosis and Haemostasis·Alessandra Borgognone, Fabio Maria Pulcinelli
Nov 13, 2014·Frontiers in Cellular Neuroscience·Winfried NeuhausCarola Förster
May 5, 2021·The AAPS Journal·Austin Sun, Joanne Wang

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