Papaverine inhibits bile acid excretion in isolated perfused rat liver.
We investigated the effects of papaverine on bile acid excretion into bile in the presence of infusions of taurocholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid and taurodehydrocholic acid in a single-pass, isolated perfused rat liver model. Although continuous infusion of papaverine (1.6 mumol/min) did not reduce bile acid excretion in the presence of low-dose (1.0 mumol/min) infusions of taurocholic acid or tauroursodeoxycholic acid, papaverine significantly inhibited biliary excretion of bile acids in the presence of low-dose taurochenodeoxycholic acid (-50%) and high-dose (3.0 mumol/min) taurocholic acid (-54%), tauroursodeoxycholic acid (-37%) and taurodehydrocholic acid (-31%). During continuous infusion of taurocholic acid (3 mumol/min), a 15-min infusion of papaverine (3.2 mumol/min) reduced bile acid excretion significantly; however, total uptake of bile acid was slightly decreased by the papaverine infusion. Bile acid excretion increased over the baseline value after the papaverine infusion was stopped and then returned to baseline. These results suggest that papaverine does not affect the uptake phase of bile acids at the sinusoidal membrane but may affect the intracellular transport phase or the excretory phase at the bile canalicular membrane. When taurocholic acid was infused at a constant rate of 3 mumol/min for 20 min without papaverine and then stopped, bile acid excretion decreased gradually and was nearly zero by 52 min. Cumulative bile acid excretion in the 52 min after the end of the infusion reached 3.3 +/- 0.2 mumol/gm liver and represented the storage capacity of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Kumai
T
T
First Department of Internal Medicine, School of Medicine, Nagoya City University, Japan.
Hoshino
M
M
Hayakawa
T
T
Higashi
K
K
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010208:Papaverine / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D001647:Bile Acids and Salts; D014667:Vasopressins; D013656:Taurocholic Acid; D010208:Papaverine; D002118:Calcium