Publication

The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α-adrenoceptor

Nakladal, D., Buikema, H., Romero, A. R., Lambooy, S. P. H., Bouma, J., Krenning, G., Vogelaar, P., van der Graaf, A. C., Groves, M. R., Kyselovic, J., Henning, R. H. & Deelman, L. E., 9-Jan-2019, In : Scientific Reports. 9, 1, 11 p., 13.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Nakladal, D., Buikema, H., Romero, A. R., Lambooy, S. P. H., Bouma, J., Krenning, G., ... Deelman, L. E. (2019). The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α-adrenoceptor. Scientific Reports, 9(1), [13]. https://doi.org/10.1038/s41598-018-36788-0

Author

Nakladal, D. ; Buikema, H. ; Romero, A. Reyes ; Lambooy, S. P. H. ; Bouma, J. ; Krenning, G. ; Vogelaar, P. ; van der Graaf, A. C. ; Groves, M. R. ; Kyselovic, J. ; Henning, R. H. ; Deelman, L. E. / The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α-adrenoceptor. In: Scientific Reports. 2019 ; Vol. 9, No. 1.

Harvard

Nakladal, D, Buikema, H, Romero, AR, Lambooy, SPH, Bouma, J, Krenning, G, Vogelaar, P, van der Graaf, AC, Groves, MR, Kyselovic, J, Henning, RH & Deelman, LE 2019, 'The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α-adrenoceptor' Scientific Reports, vol. 9, no. 1, 13. https://doi.org/10.1038/s41598-018-36788-0

Standard

The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α-adrenoceptor. / Nakladal, D.; Buikema, H.; Romero, A. Reyes; Lambooy, S. P. H.; Bouma, J.; Krenning, G.; Vogelaar, P.; van der Graaf, A. C.; Groves, M. R.; Kyselovic, J.; Henning, R. H.; Deelman, L. E.

In: Scientific Reports, Vol. 9, No. 1, 13, 09.01.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Nakladal D, Buikema H, Romero AR, Lambooy SPH, Bouma J, Krenning G et al. The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α-adrenoceptor. Scientific Reports. 2019 Jan 9;9(1). 13. https://doi.org/10.1038/s41598-018-36788-0


BibTeX

@article{7b6d0c7e7ed44d30929a092af4e32af3,
title = "The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α-adrenoceptor",
abstract = "SUL-compounds are protectants from cold-induced ischemia and mitochondrial dysfunction. We discovered that adding SUL-121 to renal grafts during warm machine reperfusion elicits a rapid improvement in perfusion parameters. Therefore, we investigate the molecular mechanisms of action in porcine intrarenal arteries (PIRA). Porcine kidneys were stored on ice overnight and perfusion parameters were recorded during treatment with SUL-compounds. Agonist-induced vasoconstriction was measured in isolated PIRA after pre-incubation with SUL-compounds. Receptor binding and calcium transients were assessed in α1-adrenoceptor (α1-AR) transgenic CHO cells. Molecular docking simulation was performed using Schr{\"o}dinger software. Renal pressure during warm reperfusion was reduced by SUL-121 (-11.9 ± 2.50 mmHg) and its (R)-enantiomer SUL-150 (-13.2 ± 2.77 mmHg), but not by the (S)-enantiomer SUL-151 (-1.33 ± 1.26 mmHg). Additionally, SUL-150 improved renal flow (16.21 ± 1.71 mL/min to 21.94 ± 1.38 mL/min). SUL-121 and SUL-150 competitively inhibited PIRA contraction responses to phenylephrine, while other 6-chromanols were without effect. SUL-150 similarly inhibited phenylephrine-induced calcium influx and effectively displaced [7-Methoxy-3H]-prazosin in CHO cells. Docking simulation to the α1-AR revealed shared binding characteristics between prazosin and SUL-150. SUL-150 is a novel α1-AR antagonist with the potential to improve renal graft perfusion after hypothermic storage. In combination with previously reported protective effects, SUL-150 emerges as a novel protectant in organ transplantation.",
author = "D. Nakladal and H. Buikema and Romero, {A. Reyes} and Lambooy, {S. P. H.} and J. Bouma and G. Krenning and P. Vogelaar and {van der Graaf}, {A. C.} and Groves, {M. R.} and J. Kyselovic and Henning, {R. H.} and Deelman, {L. E.}",
year = "2019",
month = "1",
day = "9",
doi = "10.1038/s41598-018-36788-0",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α-adrenoceptor

AU - Nakladal, D.

AU - Buikema, H.

AU - Romero, A. Reyes

AU - Lambooy, S. P. H.

AU - Bouma, J.

AU - Krenning, G.

AU - Vogelaar, P.

AU - van der Graaf, A. C.

AU - Groves, M. R.

AU - Kyselovic, J.

AU - Henning, R. H.

AU - Deelman, L. E.

PY - 2019/1/9

Y1 - 2019/1/9

N2 - SUL-compounds are protectants from cold-induced ischemia and mitochondrial dysfunction. We discovered that adding SUL-121 to renal grafts during warm machine reperfusion elicits a rapid improvement in perfusion parameters. Therefore, we investigate the molecular mechanisms of action in porcine intrarenal arteries (PIRA). Porcine kidneys were stored on ice overnight and perfusion parameters were recorded during treatment with SUL-compounds. Agonist-induced vasoconstriction was measured in isolated PIRA after pre-incubation with SUL-compounds. Receptor binding and calcium transients were assessed in α1-adrenoceptor (α1-AR) transgenic CHO cells. Molecular docking simulation was performed using Schrödinger software. Renal pressure during warm reperfusion was reduced by SUL-121 (-11.9 ± 2.50 mmHg) and its (R)-enantiomer SUL-150 (-13.2 ± 2.77 mmHg), but not by the (S)-enantiomer SUL-151 (-1.33 ± 1.26 mmHg). Additionally, SUL-150 improved renal flow (16.21 ± 1.71 mL/min to 21.94 ± 1.38 mL/min). SUL-121 and SUL-150 competitively inhibited PIRA contraction responses to phenylephrine, while other 6-chromanols were without effect. SUL-150 similarly inhibited phenylephrine-induced calcium influx and effectively displaced [7-Methoxy-3H]-prazosin in CHO cells. Docking simulation to the α1-AR revealed shared binding characteristics between prazosin and SUL-150. SUL-150 is a novel α1-AR antagonist with the potential to improve renal graft perfusion after hypothermic storage. In combination with previously reported protective effects, SUL-150 emerges as a novel protectant in organ transplantation.

AB - SUL-compounds are protectants from cold-induced ischemia and mitochondrial dysfunction. We discovered that adding SUL-121 to renal grafts during warm machine reperfusion elicits a rapid improvement in perfusion parameters. Therefore, we investigate the molecular mechanisms of action in porcine intrarenal arteries (PIRA). Porcine kidneys were stored on ice overnight and perfusion parameters were recorded during treatment with SUL-compounds. Agonist-induced vasoconstriction was measured in isolated PIRA after pre-incubation with SUL-compounds. Receptor binding and calcium transients were assessed in α1-adrenoceptor (α1-AR) transgenic CHO cells. Molecular docking simulation was performed using Schrödinger software. Renal pressure during warm reperfusion was reduced by SUL-121 (-11.9 ± 2.50 mmHg) and its (R)-enantiomer SUL-150 (-13.2 ± 2.77 mmHg), but not by the (S)-enantiomer SUL-151 (-1.33 ± 1.26 mmHg). Additionally, SUL-150 improved renal flow (16.21 ± 1.71 mL/min to 21.94 ± 1.38 mL/min). SUL-121 and SUL-150 competitively inhibited PIRA contraction responses to phenylephrine, while other 6-chromanols were without effect. SUL-150 similarly inhibited phenylephrine-induced calcium influx and effectively displaced [7-Methoxy-3H]-prazosin in CHO cells. Docking simulation to the α1-AR revealed shared binding characteristics between prazosin and SUL-150. SUL-150 is a novel α1-AR antagonist with the potential to improve renal graft perfusion after hypothermic storage. In combination with previously reported protective effects, SUL-150 emerges as a novel protectant in organ transplantation.

U2 - 10.1038/s41598-018-36788-0

DO - 10.1038/s41598-018-36788-0

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 13

ER -

ID: 73936821