Transport of guanidine in rabbit intestinal brush-border membrane vesicles

Abstract

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)

Characterization of Renal Brush-Border and Basolateral Membrane Transporters for Organic Cations

“…A similar process has also been found in BBMV from small intestine [64] and placenta [65], neither of which display TEA/H+ exchange activity. The role of this process in the renal handling of OCs is not clear, although it does display a modest inhibitory interaction with several polyamines [64],…”

Intestinal Absorption of Drugs Mediated by Drug Transporters: Mechanisms and Regulation

“…76) The data showed that an outward H ＋ gradient serves as the driving force for procainamide uptake by intestinal brush-border membrane vesicles. This H ＋ gradient-dependent transport system speciˆcal-ly recognizes tertiary amines and is diŠerent from previously characterized H ＋ W guanidine antiport system 77) and H ＋ W thiamine antiport system. 78) Taken together, theseˆndings clearly indicate that organic cations with N, N-dimethyl or N, N-diethyl moieties such as diphenhydramine and procainamide are transported by a novel H ＋ W tertiary amine antiport system in the intestinal brush-border membrane.…”

Molecular and Cellular Physiology of Renal Organic Cation and Anion Transport

“…However, despite the evidence supporting an OC/H ϩ exchanger mode of activity for OCTN1, it is not clear that this cloned transporter is the process that dominates transport activity as measured in isolated renal luminal membranes. OC/H ϩ exchange activity as functionally expressed in renal cells, or more specifically, mediated exchange of TEA for H ϩ , appears to be restricted to the kidney and the liver (299); it is not found in the placenta or intestine, although both of these organs do express a transporter that mediates exchange of guanidine for H ϩ (121,289). OCTN1, however, is expressed in many tissues, including the placenta and intestine (538).…”