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A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions

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A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions. / Nielsen, Carsten Uhd; Rasmussen, Rune N; Mo, Junying; Noori, Benafsha; Lagunas, Candela; Holm, René; Vestergaard, Martha Kampp Nøhr.

I: Molecular Pharmaceutics, Bind 13, Nr. 9, 06.09.2016, s. 3119-29.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Nielsen, CU, Rasmussen, RN, Mo, J, Noori, B, Lagunas, C, Holm, R & Vestergaard, MKN 2016, 'A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions', Molecular Pharmaceutics, bind 13, nr. 9, s. 3119-29. https://doi.org/10.1021/acs.molpharmaceut.6b00330

APA

Nielsen, C. U., Rasmussen, R. N., Mo, J., Noori, B., Lagunas, C., Holm, R., & Vestergaard, M. K. N. (2016). A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions. Molecular Pharmaceutics, 13(9), 3119-29. https://doi.org/10.1021/acs.molpharmaceut.6b00330

Vancouver

Nielsen CU, Rasmussen RN, Mo J, Noori B, Lagunas C, Holm R o.a. A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions. Molecular Pharmaceutics. 2016 sep 6;13(9):3119-29. https://doi.org/10.1021/acs.molpharmaceut.6b00330

Author

Nielsen, Carsten Uhd ; Rasmussen, Rune N ; Mo, Junying ; Noori, Benafsha ; Lagunas, Candela ; Holm, René ; Vestergaard, Martha Kampp Nøhr. / A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions. I: Molecular Pharmaceutics. 2016 ; Bind 13, Nr. 9. s. 3119-29.

Bibtex

@article{eaf32bd577a64ad3b1c8d4ceeec30cfe,
title = "A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions",
abstract = "Ibuprofen is a widely used drug. It has been identified as an inhibitor of several transporters, but it is not clear if ibuprofen is a substrate of any transporter itself. In the present work, we have characterized a transporter of ibuprofen, which is upregulated by hyperosmotic culture conditions in Madin-Darby canine kidney I (MDCK I) renal cells. [(3)H]-Ibuprofen uptake rate was measured in MDCK I cell cultured under normal (300 mOsm) and hyperosmotic (500 mOsm) conditions. Hyperosmotic conditions were obtained by supplementing urea, NaCl, mannitol, or raffinose to culture medium. The effect of increased osmolarity was investigated for different incubation times. [(3)H]-Ibuprofen uptake in MDCK I cells was upregulated by hyperosmotic culture condition, and was saturable with a Km value of 0.37 ± 0.08 μM and a Vmax of 233.1 ± 17.2 pmol· cm(-2)· min(-1). Racemic [(3)H]-ibuprofen uptake could be inhibited by (R)-(-)- and (S)-(+)-ibuprofen with IC50 values of 19 μM (Log IC50 1.39 ± 0.34) and 0.47 μM (Log IC50 -0.36 ± 0.41), respectively. Furthermore, the [(3)H]-ibuprofen uptake rate was increased by decreased extracellular pH but not dependent on Na(+) or Cl(-) ions. The mRNA of Mct1, -2, -4, and -6 as well as Oat1 and -3 were not upregulated by hyperosmolarity. Our findings present strong evidence for the presence of a yet unknown ibuprofen transporter in MDCK I cells. The transporter was upregulated under hyperosmotic culture conditions, and the present study is therefore a starting point for identification of the molecular correlate and potential impact on ibuprofen disposition.",
keywords = "Journal Article",
author = "Nielsen, {Carsten Uhd} and Rasmussen, {Rune N} and Junying Mo and Benafsha Noori and Candela Lagunas and Ren{\'e} Holm and Vestergaard, {Martha Kampp N{\o}hr}",
year = "2016",
month = "9",
day = "6",
doi = "10.1021/acs.molpharmaceut.6b00330",
language = "English",
volume = "13",
pages = "3119--29",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "9",

}

RIS

TY - JOUR

T1 - A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions

AU - Nielsen, Carsten Uhd

AU - Rasmussen, Rune N

AU - Mo, Junying

AU - Noori, Benafsha

AU - Lagunas, Candela

AU - Holm, René

AU - Vestergaard, Martha Kampp Nøhr

PY - 2016/9/6

Y1 - 2016/9/6

N2 - Ibuprofen is a widely used drug. It has been identified as an inhibitor of several transporters, but it is not clear if ibuprofen is a substrate of any transporter itself. In the present work, we have characterized a transporter of ibuprofen, which is upregulated by hyperosmotic culture conditions in Madin-Darby canine kidney I (MDCK I) renal cells. [(3)H]-Ibuprofen uptake rate was measured in MDCK I cell cultured under normal (300 mOsm) and hyperosmotic (500 mOsm) conditions. Hyperosmotic conditions were obtained by supplementing urea, NaCl, mannitol, or raffinose to culture medium. The effect of increased osmolarity was investigated for different incubation times. [(3)H]-Ibuprofen uptake in MDCK I cells was upregulated by hyperosmotic culture condition, and was saturable with a Km value of 0.37 ± 0.08 μM and a Vmax of 233.1 ± 17.2 pmol· cm(-2)· min(-1). Racemic [(3)H]-ibuprofen uptake could be inhibited by (R)-(-)- and (S)-(+)-ibuprofen with IC50 values of 19 μM (Log IC50 1.39 ± 0.34) and 0.47 μM (Log IC50 -0.36 ± 0.41), respectively. Furthermore, the [(3)H]-ibuprofen uptake rate was increased by decreased extracellular pH but not dependent on Na(+) or Cl(-) ions. The mRNA of Mct1, -2, -4, and -6 as well as Oat1 and -3 were not upregulated by hyperosmolarity. Our findings present strong evidence for the presence of a yet unknown ibuprofen transporter in MDCK I cells. The transporter was upregulated under hyperosmotic culture conditions, and the present study is therefore a starting point for identification of the molecular correlate and potential impact on ibuprofen disposition.

AB - Ibuprofen is a widely used drug. It has been identified as an inhibitor of several transporters, but it is not clear if ibuprofen is a substrate of any transporter itself. In the present work, we have characterized a transporter of ibuprofen, which is upregulated by hyperosmotic culture conditions in Madin-Darby canine kidney I (MDCK I) renal cells. [(3)H]-Ibuprofen uptake rate was measured in MDCK I cell cultured under normal (300 mOsm) and hyperosmotic (500 mOsm) conditions. Hyperosmotic conditions were obtained by supplementing urea, NaCl, mannitol, or raffinose to culture medium. The effect of increased osmolarity was investigated for different incubation times. [(3)H]-Ibuprofen uptake in MDCK I cells was upregulated by hyperosmotic culture condition, and was saturable with a Km value of 0.37 ± 0.08 μM and a Vmax of 233.1 ± 17.2 pmol· cm(-2)· min(-1). Racemic [(3)H]-ibuprofen uptake could be inhibited by (R)-(-)- and (S)-(+)-ibuprofen with IC50 values of 19 μM (Log IC50 1.39 ± 0.34) and 0.47 μM (Log IC50 -0.36 ± 0.41), respectively. Furthermore, the [(3)H]-ibuprofen uptake rate was increased by decreased extracellular pH but not dependent on Na(+) or Cl(-) ions. The mRNA of Mct1, -2, -4, and -6 as well as Oat1 and -3 were not upregulated by hyperosmolarity. Our findings present strong evidence for the presence of a yet unknown ibuprofen transporter in MDCK I cells. The transporter was upregulated under hyperosmotic culture conditions, and the present study is therefore a starting point for identification of the molecular correlate and potential impact on ibuprofen disposition.

KW - Journal Article

U2 - 10.1021/acs.molpharmaceut.6b00330

DO - 10.1021/acs.molpharmaceut.6b00330

M3 - Journal article

C2 - 27396755

VL - 13

SP - 3119

EP - 3129

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 9

ER -

ID: 169360490