Transendothelial Transport of Low-Density Lipoprotein and Albumin Across the Rat Peritoneum in vivo: Effects of the Transcytosis Inhibitors NEM and Filipin

Abstract

This study was performed to investigate the mechanisms responsible for the transport of albumin and low-density lipoprotein (LDL) across capillary walls in vivo. To separate transcytosis from passive, ‘porous’ transport, we tested the effects of the transcytosis inhibitors N-ethylmaleimide (NEM) and filipin given intraperitoneally on the peritoneal capillary clearance of LDL and albumin in anesthetized rats undergoing peritoneal dialysis. Radiolabeled human albumin or LDL was given intra-arterially, and ⁵¹Cr-EDTA was infused intravenously. A 2-hour peritoneal dialysis dwell was performed using 16 ml of conventional 1.36% glucose-based dialysis fluid. The clearance of LDL and albumin to the dialysate and the peritoneal mass transfer coefficient for ⁵¹Cr-EDTA were assessed. Following intraperitoneal NEM incubations (0.5–5 mM), there were marked increases in the peritoneal transport of albumin and LDL for NEM doses exceeding 1 mM. For lower NEM doses, there were no reductions in clearance. Filipin incubations (0.2–4 µg/ml) did not affect the clearance of either macromolecule. In conclusion, neither NEM nor filipin caused reductions in albumin or LDL clearance across the peritoneal capillaries. The present data clearly show that NEM and filipin are unsuitable as transcytosis inhibitors in vivo.