Transport von Paraaminohippursäure, Furosemid, Hydrochlorothiazid, Cimetidin, 11-Deoxycorticosteron und Taurocholat an der basolateralen Membran proximaler Nierentubuli

The renal basolateral transport system is an efficient system for secretion of a wide range of different drugs. One important part of this system is the organic anion transport system (OATS1), which is known for its wide range of substrate-specifity. Previous studies could demonstrate the interaction of a variety of substrates with OATS1, but could not demonstrate the translocation of those substrates into the tubular cell. Therefore, in the present study, the basolateral transport rate of different substrates (p-aminohippurate (PAH), furosemide, hydrochlorothiazide (HCT), cimetidine, 11-deoxycorticosteron and taurocholate) was determined on non-perfused proximal S2-Segments, microdissected from rabbit kidneys without use of enzymatic agents. To measure the transport rate, we took advantage of the finding, that OATS1 acts as a counter-transporter, which exchanges PAH (the classical substrate for this transport system) and other drugs with dicarboxylates (glutarate or a-ketoglutarate). Hence, the stimulatory effect of a drug on the 14C-glutarate efflux-rate of 14C-glutarate preloaded S2-segments is a measure of its translocation across the basolateral cell membrane. The efflux rate of 14C-glutarate was determined in presence of the investigated drugs by comparing the accumulation ratio in the tubular cells in presence of the drug and with control conditions. In presence of PAH (1000 µmol) and furosemide (400 µmol), a significantly (p=0,032 and p=0.0838) efflux-rate of 14C-glutarate could be demonstrated. These findings indicate, that PAH and furosemide are transported by the renal basolateral transport system for organic anions, just as Taurocholate (1000 µmol), which slightly stimulated the efflux of 14C-glutarate. Hydrochlorothiazide (1400 µmol), Cimetidine (98 µmol) and 11-Deoxycorticosteron (70 µmol) did not stimulate the 14C-glutarate efflux. It is concluded, that HCT, cimetidine and 11-deoxycorticosteron are not translocated by the renal basolateral transport system for organic anions, but from another transport system of the kidney.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2002

Author dc:creator

• Haßler, Martin Alexander

Contributors dc:contributor

• Greven, Joachim
• Heintz, Joachim

• info:eu-repo/classification/ddc/610
• Medizin

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-119274%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:57216