Transcellular transport of creatinine in renal tubular epithelial cell line LLC-PK1.
OBJECTIVE
Creatinine is excreted into urine via tubular secretion in addition to glomerular filtration. In the present study, characteristics of the creatinine transport in renal epithelial cells were investigated.


METHODS
The transcellular transport and accumulation of [14C]creatinine and [14C]tetraethylammonium (TEA) were assessed using LLC-PK1 cell monolayers cultured on porous membrane filters.


RESULTS
[14C]Creatinine was transported directionally from the basolateral to apical side of LLC-PK1 cell monolayers. Basolateral uptake of [14C]creatinine was dependent on membrane potential, and was saturable with apparent K(m) and V(max) values of 13.2+/-2.8 mM and 13.1+/-3.1 nmol/mg protein/5 min, respectively. Concomitant administration of organic cations (1 mM) such as cimetidine, quinidine and trimethoprim inhibited both the transcellular transport and accumulation of [14C]creatinine. Furthermore, apical excretion of [14C]creatinine was not dependent on acidification of the apical medium.


CONCLUSIONS
Creatinine was subjected to directional transport across renal epithelial cells from the basolateral to apical side. The organic cation transporter should be involved in the basolateral uptake of creatinine.
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Yumiko
Y
Urakami
Naoko
N
Kimura
Masahiro
M
Okuda
Satohiro
S
Masuda
Toshiya
T
Katsura
Ken-ichi
K
Inui
D000818:Animals; D000838:Anions / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002412:Cations / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003404:Creatinine / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D018374:LLC-PK1 Cells; D008564:Membrane Potentials; D013552:Swine; D019789:Tetraethylammonium / Q000378:metabolism; D014295:Trimethoprim / Q000494:pharmacology
D000838:Anions; D002412:Cations; D019789:Tetraethylammonium; D002927:Cimetidine; D014295:Trimethoprim; D003404:Creatinine