Differential sensitivity of organic anion transporters in rat renal brush-border membrane to diethyl pyrocarbonate.
The effect of various chemical modifiers on p-aminohippurate (PAH) uptake by a potential-sensitive system and by an anion exchanger was studied in rat renal brush-border membrane vesicles. Among various chemical modifiers, diethyl pyrocarbonate (DEPC) selectively inhibited potential-sensitive PAH uptake but not the uptake by the anion exchanger. The inhibitory effect of DEPC on potential-sensitive PAH uptake was not due to the facilitated dissipation of membrane potential, which was evidenced by the studies with a potential-sensitive fluorescence dye diS-C3(5). The potential-sensitive PAH uptake was inhibited by DEPC in a concentration-dependent manner, and kinetic analysis showed that the decreased uptake of PAH in DEPC-treated vesicles was due to the decrease of Vmax. The inhibition of the PAH uptake was protected by the presence of organic anions during the DEPC treatment. These findings indicate that PAH transport by the potential-sensitive system and by the anion exchanger is mediated by structurally distinct transporters. Amino acid residue(s) modified by DEPC, most likely a histidine residue, should play an important role in the potential-sensitive transport of PAH in rat renal brush-border membrane.
Takano
M
M
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Nagai
J
J
Okano
T
T
Hirozane
K
K
Yasuhara
M
M
Hori
R
R
D000818:Animals; D017920:Antiporters / Q000187:drug effects* / Q000378:metabolism; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D008871:Microvilli / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D010130:p-Aminohippuric Acid / Q000378:metabolism
D017920:Antiporters; D004047:Diethyl Pyrocarbonate; D010130:p-Aminohippuric Acid