Partial characterization of mechanism(s) by which sulphobromophthalein reduces biliary lipid secretion.
This study was performed to explore the mechanisms by which sulphobromophthalein (BSP) reduces the secretion of biliary lipid using Sprague-Dawley rats (SDR) and mutant rats with congenital conjugated hyperbilirubinaemia bred from SDR (EHBR). We infused the bile-salt-pool-depleted rats with sodium taurocholate at a constant rate of 160 nmol/min per 100 g body wt. with BSP (12.5, 25 and 50 nmol/min per 100 g body wt.) or BSP-GSH (12.5, 25 and 50 nmol/min per 100 g body wt.). The biliary secretion of BSP and BSP-GSH was markedly impaired in EHBR as compared with that in SDR. BSP reduced the biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting the secretion of bile salts and composition of fatty acids in phospholipids in SDR, but had no effect on lipid secretion in EHBR. In contrast, BSP-GSH had no such effect on biliary lipids, either in the SDR or EHBR. In addition, the amount of BSP in the liver of EHBR was in the same range as that of SDR. Therefore it is unlikely that an intracellular mechanism is involved in the phenomenon of uncoupling by BSP. We conclude that the uncoupling of biliary lipids from bile-salt secretion by BSP occurs at the level of the bile canaliculus following the secretion of unconjugated BSP.
Yamashita
G
G
First Department of Internal Medicine, Hiroshima University Medical School of Medicine, Japan.
Tazuma
S
S
Horikawa
K
K
Aihara
N
N
Ochi
H
H
Teramen
K
K
Yamashita
Y
Y
Sasaki
M
M
Ohya
T
T
Kajiyama
G
G
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000493:pharmacokinetics / Q000494:pharmacology; D006932:Hyperbilirubinemia / Q000503:physiopathology*; D007700:Kinetics; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D013448:Sulfobromophthalein / Q000493:pharmacokinetics / Q000494:pharmacology*
D013448:Sulfobromophthalein; C035816:(sulfobromophthalein)glutathione conjugate; D005978:Glutathione