Uptake of lopanoic Acid and Its Glucuronide Conjugate by Rat Hepatocytes in Primary Culture 1

Abstract

Abstract

Uptake of iopanoic acid (IOP) and iopanoate glucuronide (IOP-G) was studied in 3-day primary cultures of rat hepatocytes isolated by the collagenase perfusion method. ¹²⁵I activity of cells after incubation with ¹²⁵I-IOP (10-100 μM) and ¹²⁵I-IOP-G (10-100 μM) was used as a measure of uptake. At each concentration, uptake was linear for the first 45 sec. In the absence of albumin, the initial uptake velocity was directly proportional to the concentration or IOP or IOP-G and was nonsaturable up to 100 μM. The calculated uptake rate constants for IOP and for IOP-G were 0.059 and 0.048 nmole/(mg protein · min · μM), respectively. IOP uptake was not inhibited by sodium taurocholate nor by the contrast agents iodipamide, ipodate, and iopronic acid. The data indicate that the enhancement of IOP excretion by bile salts noted in vivo does not occur at the uptake step and that the hepatic uptake of both IOP and IOP-G in the absence of albumin is limited by diffusion.