Effect of Renal Ischemia on Organic Anion and Cation Transport in Rabbit Proximal Tubule

Abstract

The uptake of organic anion, ρ-aminohippurate (PAH), and organic cation, tetraethylammonium (TEA), was measured in cortical slices and plasma membrane vesicles isolated from the proximal tubule of ischemic rabbit kidneys. The uptake of PAH or TEA in cortical slices increased after 30 or 60 min of ischemia. When the kidneys were reperfused for 30 min, the uptake of organic ions returned to control levels. When ischemic (60 min) slices were preincubated for 120 min in an oxygenated medium, the stimulatory effect of ischemia on organic ion uptake was not observed. The PAH uptake by basolateral membrane vesicles and brush border membrane vesicles (BBMV) was not altered following 60 min of ischemia. However, the TEA uptake by BBMV but not basolateral membrane vesicles was significantly reduced. The dissipation rate of H⁺ gradient across the BBMV was similar in control and ischemic kidneys. The V_max for TEA transport in BBMV isolated from ischemic kidneys was significantly reduced, but the K_mwas not altered. These results indicate that the organic cation secretory system is more vulnerable to ischemia than the organic anion secretory system in the rabbit renal proximal tubule.

Molecular cloning of rabbit organic cation transporter rbOCT2 and functional comparisons with rbOCT1

“…Secretion and reabsorption of organic cations have been described in renal proximal tubules but may also occur in distal tubules or collecting ducts (1,2,6,24). The mechanisms mediating tubular secretion have been intensively studied in various experimental preparations from rabbit kidney, including perfused (9,24,38) and nonperfused (5,10,15,38) tubules, apical (12,26,29,44,45) and basolateral (28,39,44) membrane vesicles, and isolated tissue slices (21). Results from these studies identified two distinct functional classes of organic cation transporter (OCT): one localized at the basolateral membrane that is stimulated by the inside-negative membrane potential of proximal cells and the other at the brush-border membrane that is stimulated by an inwardly directed proton gradient (35).…”