Abstract
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 hems oxygenase inhibitor, on the biliary transport were tested in perfused rat liver. Perfusion of 1 μM 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 μM CO, ZnPP-elicited choleresis, decreases in vascular conductance, and cGMP levels were all attenuated. Treatment with 1 μM 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.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
| Volume | 272 |
| Issue number | 5 35-5 |
| Publication status | Published - 1997 May |
| Externally published | Yes |
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Keywords
- Adenosine 5'-triphosphate
- Bile transport
- Guanosine 3',5'-cyclic monophosphate
- Heme oxygenase
- Nitric oxide
ASJC Scopus subject areas
- Gastroenterology
- Physiology
- Physiology (medical)
Cite this
Endogenous carbon monoxide suppression stimulates bile acid-dependent biliary transport in perfused rat liver. / Sano, Tsuyoshi; Shiomi, Masaya; Wakabayashi, Yoshiyuki; Shinoda, Yuichi; Goda, Nobuhito; Yamaguchi, Tokio; Nimura, Yuji; Ishimura, Yuzuru; Suematsu, Makoto.
In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 272, No. 5 35-5, 05.1997.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endogenous carbon monoxide suppression stimulates bile acid-dependent biliary transport in perfused rat liver
AU - Sano, Tsuyoshi
AU - Shiomi, Masaya
AU - Wakabayashi, Yoshiyuki
AU - Shinoda, Yuichi
AU - Goda, Nobuhito
AU - Yamaguchi, Tokio
AU - Nimura, Yuji
AU - Ishimura, Yuzuru
AU - Suematsu, Makoto
PY - 1997/5
Y1 - 1997/5
N2 - 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 hems oxygenase inhibitor, on the biliary transport were tested in perfused rat liver. Perfusion of 1 μM 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 μM CO, ZnPP-elicited choleresis, decreases in vascular conductance, and cGMP levels were all attenuated. Treatment with 1 μM 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.
AB - 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 hems oxygenase inhibitor, on the biliary transport were tested in perfused rat liver. Perfusion of 1 μM 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 μM CO, ZnPP-elicited choleresis, decreases in vascular conductance, and cGMP levels were all attenuated. Treatment with 1 μM 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.
KW - Adenosine 5'-triphosphate
KW - Bile transport
KW - Guanosine 3',5'-cyclic monophosphate
KW - Heme oxygenase
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=0030957706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030957706&partnerID=8YFLogxK
M3 - Article
C2 - 9176239
AN - SCOPUS:0030957706
VL - 272
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0193-1849
IS - 5 35-5
ER -