Bile duct epithelia regulate biliary bicarbonate excretion in normal rat liver  Keiji Hirata, Michael H. Nathanson  Gastroenterology  Volume 121, Issue 2, Pages 396-406 (August 2001) DOI: 10.1053/gast.2001.26280 Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.1 Secretin increases biliary bicarbonate concentration in a dose-dependent fashion.Secretin was infused via the hepatic artery in the isolated bivascularly perfused rat liver.Values here and in subsequent figures are means ± SD. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.2 The effects of secretin on biliary bicarbonate concentration are attenuated when secretin is infused via the portal vein rather than the hepatic artery. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.3 Dose-response curves for secretin-induced bicarbonate excretion.Data represent the net increase in bicarbonate concentration observed when secretin is administered via the hepatic artery (Figure 1) or the portal vein (Figure 2). Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.4 Effect of secretin on bile flow in the bivascularly perfused rat liver.Secretin does not affect the rate of bile flow when it is infused via either (A) the hepatic artery or (B) the portal vein. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.5 ACh increases biliary bicarbonate concentration when it is infused via the hepatic artery but not the portal vein in the bivascularly perfused rat liver. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.6 ACh transiently decreases bile flow regardless of whether it is infused via the hepatic artery or portal vein in the bivascularly perfused rat liver. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.7 Effect of secretin plus ACh on biliary bicarbonate concentration.Secretin, ACh, or both were infused via the hepatic artery in the isolated bivascularly perfused rat liver.Simultaneous infusion of secretin (1 nmol/L) plus ACh (10 μmol/L) increased biliary bicarbonate concentration to the same extent as either agent alone.The tracings of secretin (1 nmol/L) or ACh (10 μmol/L) alone are from Figures 1 and 5. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.8 Cyclosporin A does not alter the effects of secretin (1 nmol/L) plus ACh (10 μmol/L) on either (A) bicarbonate excretion or (B) bile flow.In each tracing, the agents are infused via the hepatic artery.The tracing of secretin plus ACh without cyclosporin A in A is from Figure 7. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.9 Synergy between secretin (1 nmol/L) and ACh (10 μmol/L) depends on the order of administration.(A) ACh potentiates the effect of secretin on bicarbonate excretion, but only when secretin is administered first.(B) The synergistic effect of secretin plus ACh is blocked by cyclosporin A. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.10 The effect of ACh (10 μmol/L) but not secretin (1 nmol/L) on bicarbonate excretion is inhibited by DIDS (100 μmol/L).(A) Direct comparison of the effects of DIDS, DIDS + ACh, and DIDS + secretin.Each agent was infused via the hepatic artery.(B) DIDS blocks ACh-induced bicarbonate excretion.ACh data from Figures 5 and 10A are replotted to show the change from baseline bicarbonate excretion when control data are subtracted at each time point.(C) DIDS has no effect on secretin-induced bicarbonate excretion.Secretin data from Figures 1 and 10A are replotted to show the change from baseline bicarbonate excretion when control data are subtracted at each time point. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.11 DPC (100 μmol/L) inhibits the effect of both ACh (10 μmol/L) and secretin (1 nmol/L) on bicarbonate excretion.(A) Direct comparison of the effects of DPC, DPC + ACh, and DPC + secretin.Each agent was infused via the hepatic artery.(B) DPC blocks ACh-induced bicarbonate excretion.ACh data from Figures 5 and 11A are replotted to show the change from baseline bicarbonate excretion when control data are subtracted at each time point.(C) DPC inhibits but does not block secretin-induced bicarbonate excretion.Secretin data from Figures 1 and 11A are replotted to show the change from baseline bicarbonate excretion when control data are subtracted at each time point. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.12 NPPB (50 μmol/L) inhibits the effect of both ACh (10 mmol/L) and secretin (1 nmol/L) on bicarbonate excretion.(A) Direct comparison of the effects of NPPB, NPPB + ACh, and NPPB + secretin.Each agent was infused via the hepatic artery.(B) NPPB blocks ACh-induced bicarbonate excretion.ACh data from Figures 5 and 12A are replotted to show the change from baseline bicarbonate excretion when control data are subtracted at each time point.(C) NPPB inhibits but does not block secretin-induced bicarbonate excretion.Secretin data from Figures 1 and 12A are replotted to show the change from baseline bicarbonate excretion when control data are subtracted at each time point. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig.13 Effects of glucagon and vasopressin on (A) bile flow and (B) biliary bicarbonate excretion in the isolated perfused rat liver.In these experiments, glucagon or vasopressin were infused via the portal vein, and the hepatic artery was not cannulated. Gastroenterology 2001 121, 396-406DOI: (10.1053/gast.2001.26280) Copyright © 2001 American Gastroenterological Association Terms and Conditions