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Organic cation transporters translocate ß-blockers and fluoroquinolones and are down-regulated after experimental kidney transplantation (CROSBI ID 615091)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Schlatter E ; Edemir B ; Vollenbröker, B ; Gabriëls, G ; Brzica, Hrvoje ; Sabolić, Ivan ; Pietig, G ; Ciarimboli, G Organic cation transporters translocate ß-blockers and fluoroquinolones and are down-regulated after experimental kidney transplantation // Kongress für Nephrologie. 2014

Podaci o odgovornosti

Schlatter E ; Edemir B ; Vollenbröker, B ; Gabriëls, G ; Brzica, Hrvoje ; Sabolić, Ivan ; Pietig, G ; Ciarimboli, G

engleski

Organic cation transporters translocate ß-blockers and fluoroquinolones and are down-regulated after experimental kidney transplantation

Objective: Kidney transplanted patients are often treated with immunosuppressive, antihypertensive, and antibiotic drugs such as cyclosporine A (CsA), ß-blockers and fluoroquinolones, respectively. Organic cation transporters (OCT) expressed in the basolateral membrane of proximal tubules represent an important drug excretion route. Several pathological situations potentially down regulate renal transport proteins including organic cation transporters. Method: Here, the expression of OCT mRNA and protein after syngeneic and allogeneic kidney transplantation in rats with or without CsA immunosuppression and the functional interaction/transport of CsA, ß-blockers (pindolol/atenolol) and fluoroquinolones (ofloxacin/ norfloxacin) with/by rOCT1, rOCT2, hOCT1, and hOCT2 in stably transfected HEK293-cells were studied microfluorimetrically using the fluorescent substrate ASP. Results: Kidney transplantation was associated with reduced expression of rOCT1, while rOCT2 showed only reduced expression after allogeneic transplantation at day 4 after surgery. All drugs interacted subtype- and species-dependently with OCT in a concentration dependent manner. While atenolol, pindolol, and ofloxacin were transported by hOCT2, which is the main OCT in human kidneys. In contrast norfloxacin inhibited OCT transport but was not transported. CsA is also no OCT substrate, but it exerts a short-term effect on OCT-activity, changing their affinity for some substrates. In conclusion, we have demonstrated that the renal expression of OCT is specifically decreased by renal transplantation and graft rejection. Moreover, their activity is acutely down- regulated by CsA. Conclusion: These facts, together with the demonstration that some drugs commonly used in the treatment of transplant recipients are transported by the human renal hOCT2 (atenolol, pindolol, and ofloxacin), underline the importance of OCT in governing renal drug excretion, especially in situations of reduced renal function such as e.g. kidney transplantation. A detailed knowledge of the mechanisms governing renal drug excretion and drug-drug interactions is important to establish rational therapeutic protocols aimed to optimize treatment effects in patients suffering from various diseases.

organic cation transporters; kidney transplantation; cyclosporine A

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Podaci o prilogu

2014.

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objavljeno

Podaci o matičnoj publikaciji

Kongress für Nephrologie

1863-2262

Podaci o skupu

6.Jahrestagung der Deutschen Gesellschaft für Nephrologie-Kongress für Nephrologie

poster

06.09.2014-09.09.2014

Berlin, Njemačka

Povezanost rada

Temeljne medicinske znanosti