THE SINUSOIDAL EFFLUX OF DIBROMOSULFOPHTHALEIN FROM RAT-LIVER IS STIMULATED BY ALBUMIN, LIGANDIN AND FATTY-ACID-BINDING PROTEIN BUT NOT BY OTHER DIBROMOSULFOPHTHALEIN BINDING-PROTEINS

Citation
Hmj. Nijssen et al., THE SINUSOIDAL EFFLUX OF DIBROMOSULFOPHTHALEIN FROM RAT-LIVER IS STIMULATED BY ALBUMIN, LIGANDIN AND FATTY-ACID-BINDING PROTEIN BUT NOT BY OTHER DIBROMOSULFOPHTHALEIN BINDING-PROTEINS, Journal of hepatology, 21(1), 1994, pp. 29-36
Citations number
39
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
ISSN journal
01688278
Volume
21
Issue
1
Year of publication
1994
Pages
29 - 36
Database
ISI
SICI code
0168-8278(1994)21:1<29:TSEODF>2.0.ZU;2-1
Abstract
Organic anions can be excreted from the liver into the bile or back in to the general circulation (sinusoidal efflux). It has previously been shown that the net sinusoidal efflux rate of dibromosulfophthalein fr om the perfused liver into the perfusate is the result of actual efflu x from and reuptake into the liver, and can be strongly influenced by the presence of bovine serum albumin in the perfusion medium. The pres ent study investigated whether the influence of albumin on the net sin usoidal efflux process is albumin-specific or whether other binding pr oteins could have a similar effect on the sinusoidal efflux. Using a s ingle-pass liver perfusion technique and short-lasting (pulse) protein infusions, the stimulatory effect of a wide range of dibromosulfophth alein binding proteins on the sinusoidal efflux process were determine d. These experiments showed that all the serum albumins tested as well as the liver cytosolic binding proteins fatty acid binding protein an d ligandin (glutathione S-transferase) stimulated this process. The ot her proteins tested, bovine beta lactoglobulin-b, human gamma globulin and chicken egg lysozyme showed no stimulatory effect, despite relati vely high equilibrium binding of dibromosulfophthalein. No clear-cut r elationship was found between the equilibrium unbound ligand concentra tion as measured in perfusate and the stimulatory effect, suggesting a bsence of equilibrium binding in the sinusoids. Equilibrium binding of dibromosulfophthalein to chicken serum albumin and ligandin as well a s the dissociation rate constants were determined in vitro with rapid filtration techniques. Pharmacokinetic modeling using a series compart ment model showed that the stimulatory effect of these proteins could only be simulated accurately with higher values for both the associati on and dissociation rate constants compared with those determined in v itro, as was previously also found for bovine serum albumin. This may imply altered binding characteristics of the proteins during passage t hrough the liver and/or a direct effect on the carrier-mediated efflux process. (C) Journal of Hepatology.