Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary obstruction.
Renal function in the course of obstructive jaundice has been the subject of great interest; however, little is known about the expression of renal organic anion transporters. The objective of this work was to study, in rats with acute extrahepatic cholestasis, the cortical renal expression of the organic anion transporter 1 (OAT1) and the organic anion transporter 3 (OAT3), in association with the pharmacokinetics and renal excretion of furosemide (FS). Male Wistar rats underwent bile duct ligation (BDL rats). Pair-fed sham-operated rats served as controls. All studies were carried out 21 hours after surgery. Rats were anesthetized and the pharmacokinetic parameters of FS and the renal elimination of FS were determined. Afterwards, the kidneys were excised and processed for immunoblot (basolateral membrane and renal homogenates) or immunocytochemical (light microscopic and confocal immunofluorescence microscopic analysis) techniques. The systemic and renal clearance of FS as well as the excreted and secreted load of FS increased in BDL rats. In kidneys from BDL rats, immunoblotting showed a significant increase in the abundance of both OAT1 and OAT3 in homogenates from renal cortex. In basolateral membranes from kidney cortex of BDL rats, OATI abundance was also increased and OAT3 abundance was not modified. Immunocytochemical techniques confirmed these results. In conclusion, acute obstructive jaundice is associated with an upregulation of OAT1 and OAT3, which might explain, at least in part, the increased systemic and renal elimination of FS.
Brandoni
Anabel
A
Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, Argentina.
Villar
Silvina R
SR
Picena
Juan C
JC
Anzai
Naohiko
N
Endou
Hitoshi
H
Torres
Adriana M
AM
D000208:Acute Disease; D000818:Animals; D001651:Cholestasis, Extrahepatic / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D027362:Organic Anion Transport Protein 1 / Q000096:biosynthesis*; D029362:Organic Anion Transporters, Sodium-Independent / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3