Modifications in p-aminohippurate renal transport in rats with acute biliary obstruction.

BRANDONI, ANABEL; VILLAR, SILVINA RAQUEL; ANZAI, NAOHIKO; ENDOU, HITOSHI; TORRES, ADRIANA MÓNICA

Buenos Aires

Congreso; XXII Congreso Latinoamericano y I Iberoamericano de Ciencias Fisiológicas.; 2006

Sociedad Argentina de Fisiología

In rats with bile duct obstruction (BDL) we demonstrated an upregulation of the organic anion transporter 1 (OAT1) in basolateral membranes from kidney cortex (Hepatology 43: 1092-1100, 2006). OAT1 is an organic anion/dicarboxylate exchanger that plays a primary role in the tubular secretion of endogenous and exogenous organic anions. The aim of this work was to study in depth the renal organic anion transport system in BDL rats, using p-aminohippurate (PAH) as a suitable marker of the OAT1 secretory pathway. Male Wistar rats underwent bile duct ligation. Sham-operated rats served as controls. All studies were carried out 21 hours after surgery. By conventional clearance techniques, PAH renal clearance and the secretory maximum capacity (Tm PAH) were assayed. Kinetic parameters of 3H-PAH uptake in renal basolateral membrane vesicles (BLMV) were determined using the rapid filtration technique. At high doses, an increase in the renal clearance of PAH was observed (mL/min/100g b.w., Sham: 2.87 ± 0.09, n=7; BDL: 3.30 ± 0.15, n=8, p<0.05). Tm PAH (ug/min/100 g b.w.) increased in BDL group (n=4) to 475 ± 15 from 395 ± 16 observed in Sham rats (n=4), p < 0.05. Maximal uptake for PAH transport in BLMV (Vmax, nmoles/15sec/mg Prot.) was 6.5 ± 0.2, n=3, vs 11.9 ± 0.4, n=3, p <0.05 in Sham and BDL respectively. Michaelis-Menten constants for PAH uptake in BLMV were similar in both experimental groups. Moreover, 3H-PAH (5 uM) uptake was measured in S2 cells expressing OAT1, in the absence or in the presence of Bilirubin Ditaurate (BD 100 uM) (24h). BD addition increased 3H-PAH uptake (pmoles/min/mg Protein) from 14.51 ± 0.19 n=7 to 18.00 ± 1.26 n=7, p <0.05. The previously observed OAT1 upregulation in BDL rats might lead to the higher elimination of its transported compound, PAH and, this alteration might be mediated by the high circulating levels of bilirubin.