Endogenous carbon monoxide suppression stimulates bile acid-dependent biliary transport in perfused rat liver.
This study aimed to investigate whether carbon monoxide (CO), a product of heme oxygenase that degrades protoheme IX, serves as an endogenous modulator for biliary transport. To that end, effects of zinc protoporphyrin IX (ZnPP), a heme oxygenase inhibitor, on the biliary transport were tested in perfused rat liver. Perfusion of 1 microM ZnPP abolished detectable levels of CO in the venous perfusate and increased bile acid-dependent bile output accompanying an increased secretion of bile salts. The ZnPP-induced choleresis coincided with a reduction of tissue guanosine 3',5'-cyclic monophosphate (cGMP) levels and a decrease in vascular conductance. On administration of 2.5 microM CO, ZnPP-elicited choleresis, decreases in vascular conductance, and cGMP levels were all attenuated. Treatment with 1 microM 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) partly attenuated the ZnPP-induced choleresis in concert with repression of vascular conductance. Furthermore, treatment of the liver with methylene blue, a guanylate cyclase inhibitor, evoked a choleresis similar to that induced by ZnPP. Thus endogenous CO suppression stimulates the biliary transport in part through a cGMP-dependent mechanism.
Sano
T
T
Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan.
Shiomi
M
M
Wakabayashi
Y
Y
Shinoda
Y
Y
Goda
N
N
Yamaguchi
T
T
Nimura
Y
Y
Ishimura
Y
Y
Suematsu
M
M
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000502:physiology*; D001663:Bilirubin / Q000037:antagonists & inhibitors / Q000652:urine; D001692:Biological Transport; D002248:Carbon Monoxide / Q000037:antagonists & inhibitors*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006735:Horseradish Peroxidase / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D009599:Nitroprusside / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects
D001647:Bile Acids and Salts; D004791:Enzyme Inhibitors; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D009599:Nitroprusside; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006735:Horseradish Peroxidase; D006152:Cyclic GMP; D001663:Bilirubin