PMID- 10994628
OWN - NLM
STAT- MEDLINE
DCOM- 20010111
LR  - 20190814
IS  - 0036-5521 (Print)
IS  - 0036-5521 (Linking)
VI  - 35
IP  - 8
DP  - 2000 Aug
TI  - Intravenous bilirubin, dibromosulfophthalein, and bromosulfophthalein infusions 
      uncouple biliary phospholipid and cholesterol secretion from bile acid secretion 
      by inhibiting hepatic phosphoglycoprotein-3 activity in pigs.
PG  - 873-82
AB  - BACKGROUND: Biliary secretion of organic anions disturbs the proportional 
      relationship normally pertaining between biliary lipid and bile acid secretion. 
      The mechanism causing this uncoupling of biliary lipid from bile acid secretion 
      is incompletely understood. Impaired micellization of membrane lipids by bile due 
      to biliary contamination with organic anions or lowering of biliary bile acid 
      concentration by enhanced bile acid-independent bile flow has been proposed as 
      causative factors. Recently, we found that hepatic phosphoglycoprotein 3 (pgp3) 
      activity was reduced in pigs during bilirubin-induced uncoupling of biliary lipid 
      from bile acid secretion. Pgp3 is the phosphatidylcholine flippase in the 
      canalicular membrane sustaining biliary phospholipid secretion in pigs. This 
      investigation was undertaken to examine whether bilirubin, dibromosulfophthalein, 
      and bromosulfophthalein uncouple biliary lipid from bile acid secretion by the 
      same mechanism. METHODS/RESULTS: Hepatic bile was collected from 24 anesthetized 
      pigs before and during infusion of 0.63 micromol x kg body wt(-1) x min(-1) 
      intravenous bilirubin, dibromosulfophthalein, or bromosulfophthalein. Bile acid 
      secretion was varied by intraportal cholic acid infusion. Hepatic pgp3 expression 
      was measured by means of Western blot, using C219 antibody. Bilirubin > 
      dibromosulfophthalein > bromosulfophthalein lowered biliary lipid secretion 
      without altering hepatic pgp3 expression, increased bile acid-independent bile 
      flow (bromosulfophthalein > dibromosulfophthalein > bilirubin), and enhanced the 
      capacity of bile to micellize membrane lipids as assayed by means of erythrocyte 
      lysis. Biliary bile acid concentration did not determine biliary lipid secretion. 
      CONCLUSION: Bilirubin, dibromosulfophthalein, and bromosulfophthalein in bile 
      uncouple biliary lipid from bile acid secretion by inhibiting hepatic pgp3 
      phosphatidylcholine flippase activity, putatively through diffusing into the pgp3 
      pore.
FAU - Labori, K J
AU  - Labori KJ
AD  - Institute for Experimental Medical Research and Research Forum, Ulleval Hospital, 
      Oslo, Norway.
FAU - Bjornbeth, B A
AU  - Bjornbeth BA
FAU - Hvattum, E
AU  - Hvattum E
FAU - Lyberg, T
AU  - Lyberg T
FAU - Raeder, M G
AU  - Raeder MG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Scand J Gastroenterol
JT  - Scandinavian journal of gastroenterology
JID - 0060105
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Membrane Proteins)
RN  - 0 (Pgp3 protein, Sus scrofa)
RN  - 0 (Phospholipids)
RN  - 0C2P5QKL36 (Sulfobromophthalein)
RN  - 17199-35-8 (dibromosulphthalein)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/*antagonists & inhibitors
MH  - Animals
MH  - Bile Acids and Salts/*metabolism
MH  - Bilirubin/*pharmacology
MH  - Blotting, Western
MH  - Cholesterol/metabolism
MH  - Female
MH  - Infusions, Intravenous
MH  - Liver/*enzymology
MH  - Male
MH  - *Membrane Proteins
MH  - Models, Animal
MH  - Phospholipids/metabolism
MH  - Reference Values
MH  - Sensitivity and Specificity
MH  - Sulfobromophthalein/*pharmacology
MH  - Swine
EDAT- 2000/09/20 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/20 11:00
PHST- 2000/09/20 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/20 11:00 [entrez]
AID - 10.1080/003655200750023264 [doi]
PST - ppublish
SO  - Scand J Gastroenterol. 2000 Aug;35(8):873-82. doi: 10.1080/003655200750023264.