Regulation by physiological cations of acetylcholine transport mediated by human OCTN1 (SLC22A4). Implications in the non-neuronal cholinergic system

Life Sciences
Lorena PochiniCesare Indiveri

Abstract

This study aimed to investigate the influence of physiological ions on the transport of acetylcholine which is catalyzed by the recombinant human Organic Cation Transporter Novel 1 (hOCTN1), thus being involved in the function of the non neuronal cholinergic system. The experimental model of proteoliposomes reconstituted with the hOCTN1 transporter obtained by over-expression in E. coli has been used. Uptake and efflux of [(3)H]acetylcholine in the proteoliposome system have been followed in the presence of different cations, mimicking the cell environment. Internal K(+) stimulated, while external Na(+) strongly inhibited the uptake of [(3)H]acetylcholine in proteoliposomes. Strong inhibition was exerted also by external K(+) while Mg(2+) or sucrose had no effect. Differently, the efflux of [(3)H]acetylcholine from proteoliposomes was not influenced by external or internal Na(+) and was only marginally stimulated by internal K(+). By dose response analysis of the Na(+) inhibition, an IC(50) of 1.3 mM was derived. The kinetic analysis of the Na(+) effect revealed a competitive type of inhibition on acetylcholine uptake, i.e., Na(+) interacts with the same external binding site of acetylcholine with a Ki of 1.2 mM. Acetylcholine ...Continue Reading

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Citations

Jul 16, 2013·Current Opinion in Nephrology and Hypertension·Hermann Koepsell
Jul 24, 2014·Amino Acids·Mariafrancesca ScaliseCesare Indiveri
Jan 3, 2016·Biochimica Et Biophysica Acta·Lorena PochiniCesare Indiveri
Oct 24, 2015·FEBS Letters·Mariafrancesca ScaliseCesare Indiveri
May 6, 2015·International Immunopharmacology·Lorena PochiniCesare Indiveri
Aug 11, 2015·The International Journal of Biochemistry & Cell Biology·Lara NapolitanoCesare Indiveri
Apr 8, 2015·Chemical Research in Toxicology·Annamaria TonazziCesare Indiveri
Feb 26, 2016·Expert Opinion on Drug Delivery·Sabrina NickelCarsten Ehrhardt
Apr 12, 2015·Biochimica Et Biophysica Acta·Lara ConsoleCesare Indiveri
Apr 1, 2014·Current Opinion in Pharmacology·Wolfgang Kummer, Gabriela Krasteva-Christ
Dec 11, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Michele GalluccioCesare Indiveri
Jul 8, 2016·Journal of Clinical Pharmacology·Anna Hucke, Giuliano Ciarimboli
Dec 6, 2016·International Journal of Molecular Sciences·Maria Di BariAda Maria Tata
Jun 19, 2013·Journal of Biomolecular Screening·Lorena PochiniCesare Indiveri
Aug 27, 2013·Experimental Physiology·Anastasia A BorodinovaGalina S Sukhova
Feb 12, 2020·International Journal of Molecular Sciences·Lorena PochiniCesare Indiveri
Feb 28, 2015·Biological Research·Jie GuoXiaoxia Che

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