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.
|ジャーナル||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|出版ステータス||Published - 1997 5月|
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