Transport of guanidine in rabbit intestinal brush-border membrane vesicles.
The characteristics of guanidine uptake were studied in brush-border membrane vesicles isolated from the rabbit proximal intestine. Guanidine uptake was manyfold greater in the presence of an outward-directed H+ gradient (intracellular pH = 5.5; extracellular pH = 7.2) than in the absence of a H+ gradient (intracellular and extracellular pH = 7.2). The time course of guanidine uptake exhibited an overshoot phenomenon in the presence of the H+ gradient, indicating occurrence of uphill transport. This H+ gradient-stimulated guanidine uptake was not due to an inside-negative H+-diffusion potential because carbonyl cyanide 4-trifluoromethoxyphenylhydrazone, a protonophore, failed to have any effect on guanidine uptake. Moreover, the transient uphill transport of guanidine was observed even in voltage-clamped membrane vesicles. However, under the conditions that effectively dissipated the H+ gradient, there was no active transport of guanidine. This H+ gradient-dependent transport mechanism for guanidine is distinct from the Na+-H+ exchanger, because amiloride did not inhibit guanidine uptake even at a concentration as high as 100 microM. These data provide evidence for the presence of a guanidine-H+ antiport system in the rabbit intestinal brush-border membrane. The presence of a carrier for guanidine in these membranes is further substantiated by the trans-stimulation of the uptake of radiolabeled guanidine by unlabeled guanidine and by the inhibition of guanidine uptake by imipramine under equilibrium exchange conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Miyamoto
Y
Y
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-3331.
Ganapathy
V
V
Leibach
F H
FH
D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D019791:Guanidine; D006146:Guanidines / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D007422:Intestines / Q000648:ultrastructure*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D012964:Sodium; D019791:Guanidine; D007099:Imipramine