Influence of backward perfusion on ursodeoxycholate-induced choleresis in isolated in situ rat liver.
Ursodeoxycholate-induced bicarbonate-rich hypercholeresis was studied in isolated in situ forward- or backward-perfused rat livers. Both spontaneous bile flow and bile acid secretion were similar regardless of the direction of the perfusion. The choleretic effect of tauroursodeoxycholate infusion (400 nmol.min-1.100 g-1 body weight) was not significantly different in forward- or backward-perfused livers either. Ursodeoxycholate infusions at low rate (800 nmol.min-1.100 g-1 body weight) induced similar bile flow, bile acid output and bicarbonate output in both forward- and backward-perfused livers. Net ursodeoxycholate uptake, measured as [14C]ursodeoxycholate uptake over the bile acid infusion period (30 min), was not significantly different during forward- or backward-perfusion (4.8 and 5.1 mumol/g liver, respectively); i.e., approx. 67% of infused dose (approximately 7.5 mumol/g liver per 30 min). A 2-fold increase in the dose of ursodeoxycholate infusion (1600 nmol.min-1.100 g-1 b.wt.) induced additional enhancement in both bile flow and bicarbonate biliary secretion, but not in bile acid uptake or output, in forward-perfused livers. Moreover, infusion of the same dose of ursodeoxycholate to backward-perfused livers had a significantly lower choleretic effect (-29%, p less than 0.001) even though ursodeoxycholate uptake and biliary output were similar regardless of perfusion direction. Net ursodeoxycholate uptake, was only 2.4 mumol/g liver; i.e., approx. 16% of infused dose (approximately 15 mumol/g liver per 30 min). These findings indicate that a process related with the hepatic microanatomy may be involved in the hypercholeretic response to ursodeoxycholate.(ABSTRACT TRUNCATED AT 250 WORDS)
Perez Barriocanal
F
F
Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
Marin
J J
JJ
Dumont
M
M
Erlinger
S
S
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001646:Bile / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D013655:Taurochenodeoxycholic Acid / Q000009:adverse effects; D014580:Ursodeoxycholic Acid / Q000009:adverse effects*
D001639:Bicarbonates; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid