The transport mechanism of choline was examined using rat renal brush-
border membrane vesicles in comparison with tetraethylammonium transpo
rt. The stimulatory effect of an outward H+ gradient on choline uptake
was weak compared with that on tetraethylammonium uptake. [C-14]Tetra
ethylammonium uptake was cis-inhibited and trans-stimulated by choline
, but the effects were less pronounced than those produced by unlabele
d tetraethylammonium. [H-3]Choline uptake was trans-stimulated by unla
beled choline, but not by tetraethylammonium. An interior-negative mem
brane potential induced marked stimulation of choline uptake against i
ts concentration gradient (overshoot phenomenon), and the uptake was s
aturable with an apparent K(m) of 0.77 mM. Various compounds such as h
emicholinium-3 inhibited the choline uptake by renal brush-border memb
rane vesicles, but a sulfhydryl reagent did not. These findings sugges
t that choline can be actively transported by a carrier-mediated syste
m driven by cell interior-negative membrane potential in renal brush-b
order membrane, and this system may play an important role in the tubu
lar reabsorption of choline.