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Cationic uremic tox...
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Schophuizen, Carolien M. S.
(författare)
Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
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2013-06-29
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Springer Science and Business Media LLC,2013
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:784fc9da-ac06-42fa-ba5c-1e9377947939
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https://lup.lub.lu.se/record/4273397URI
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https://doi.org/10.1007/s00424-013-1307-zDOI
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Several organic cations, such as guanidino compounds and polyamines, have been found to accumulate in plasma of patients with kidney failure due to inadequate renal clearance. Here, we studied the interaction of cationic uremic toxins with renal organic cation transport in a conditionally immortalized human proximal tubule epithelial cell line (ciPTEC). Transporter activity was measured and validated in cell suspensions by studying uptake of the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP(+)). Subsequently, the inhibitory potencies of the cationic uremic toxins, cadaverine, putrescine, spermine and spermidine (polyamines), acrolein (polyamine breakdown product), guanidine, and methylguanidine (guanidino compounds) were determined. Concentration-dependent inhibition of ASP(+) uptake by TPA, cimetidine, quinidine, and metformin confirmed functional endogenous organic cation transporter 2 (OCT2) expression in ciPTEC. All uremic toxins tested inhibited ASP(+) uptake, of which acrolein required the lowest concentration to provoke a half-maximal inhibition (IC50 = 44 +/- 2 mu M). A Dixon plot was constructed for acrolein using three independent inhibition curves with 10, 20, or 30 mu M ASP(+), which demonstrated competitive or mixed type of interaction (K (i) = 93 +/- 16 mu M). Exposing the cells to a mixture of cationic uremic toxins resulted in a more potent and biphasic inhibitory response curve, indicating complex interactions between the toxins and ASP(+) uptake. In conclusion, ciPTEC proves a suitable model to study cationic xenobiotic interactions. Inhibition of cellular uptake transport was demonstrated for several uremic toxins, which might indicate a possible role in kidney disease progression during uremia.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Wilmer, Martijn J.
(författare)
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Jansen, Jitske
(författare)
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Gustavsson, LenaLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine(Swepub:lu)med-lgu
(författare)
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Hilgendorf, Constanze
(författare)
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Hoenderop, Joost G. J.
(författare)
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van den Heuvel, Lambert P.
(författare)
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Masereeuw, Rosalinde
(författare)
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Institutionen för translationell medicinMedicinska fakulteten
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Pflügers Archiv: Springer Science and Business Media LLC465:12, s. 1701-17140031-6768
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Ingår i:Pflügers Archiv - European Journal of Physiology: Springer Science and Business Media LLC465:12, s. 1701-17141432-2013
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