The effect of portal blood bile salt concentrations on bile salt synthesis in rat liver

Botham, Kathleen M.; Lawson, Margaret E.; Beckett, Geoffrey J.; Percy‐Robb, I. W.; Boyd, George S.

doi:10.1016/0005-2760(81)90113-2

Cited by 27 publications

(15 citation statements)

References 16 publications

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“…Moreover, the induction of bile acid formation during bile duct ligation despite an elevation ofbile acid concentrations in the liver (35) may also be explained, since under these conditions deoxycholic acid formation in the colon is prevented. The findings of the present study are also compatible with the absence offeedback regulation by primary bile acids in isolated or cultured hepatocytes (24)(25)(26), where deoxycholic acid is too toxic to allow the direct experiment. Finally, it is striking that the inhibition of synthesis by deoxycholate of different bile acids (taurocholate > taurochenodeoxycholate > tauromuricholate) follows the same order as the degree ofderepression (Fig.…”

Section: Methodssupporting

confidence: 89%

“…On the other hand, although During the phase after cessation of the infusion, a combithe various bile acids appeared to differ with respect to their nation of taurocholic acid and deoxycholic acid at lower doses choleretic effect, none clearly diminished bile flow as an indi-(254 plus 24 zmol/kg per h or 285 plus 15 ,tmol/kg per h, cation of a cholestatic effect. respectively) also inhibited nadir secretion (i.e., synthesis) of taurocholic acid by 41 and 36%, respectively (Fig.…”

Section: Methodsmentioning

confidence: 91%

“…This is quite close to the normal rate of deoxycholic acid secretion of 6 ,umol/kg per h in these animals, which is almost certainly an underestimate ofthe physiological flux to the liver. This flux is difficult to determine since data on bile acid concentrations in rat portal blood are scanty (24,42). We have therefore determined deoxycholic acid levels in postprandial rat portal serum by gas liquid chromatography and found a mean of 21.…”

Section: Methodsmentioning

confidence: 97%

“…First, bile acids failed to regulate their rates of synthesis both in isolated (24) and cultured (25,26) hepatocytes. Second, several in vivo studies in the rat, hamster, and man also were unable to confirm the feedback concept uniformly (27)(28)(29)(30)(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

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Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.

Stange¹,

Scheibner²,

Ditschuneit³

1989

J. Clin. Invest.

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Section: Methodssupporting

confidence: 89%

Section: Methodsmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.

Stange¹,

Scheibner²,

Ditschuneit³

1989

J. Clin. Invest.

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“…3 It was traditionally assumed that primary bile acids alone mediate a negative feedback control, 4,5 but this is not consistent with negative experiments in cell culture, [6][7][8] as well as in vivo in the rat. [9][10][11][12] Thus, we suggested that the more hydrophobic secondary bile acids may be more effective than the primary bile acids.…”

mentioning

confidence: 99%

Complex feedback regulation of bile acid synthesis in the hamster: The role of newly synthesized cholesterol

et al. 1999

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Hepatic bile acid synthesis is regulated by recirculating bile acids, possibly by modulating the availability of newly synthesized and preformed cholesterol. Because data in the hamster on this mechanism are lacking, we fitted these animals with an extracorporeal bile duct and administered tritiated water intraperitoneally to label newly formed cholesterol. After interruption of the enterohepatic circulation, physiological and double-physiological doses of conjugated cholate (25 or 50 mol/100 g · h) or of unconjugated deoxycholate (6 or 12 mol) were infused intraduodenally for 54 hours and compared with controls. De novo and preformed cholesterol directly secreted into bile or used for cholate and chenodeoxycholate synthesis were quantitated by high-pressure liquid chromatography (HPLC)-liquid scintillation. Directly after depletion of the bile acid pool (6-9 hours) at nearly physiological conditions, chenodeoxycholate synthesis was significantly reduced by cholate and deoxycholate by up to 45% to 51%, whereas cholate formation decreased by Ϸ22% during deoxycholate. This short-term effect was mainly mediated by reduced synthesis from preformed cholesterol. After long-term bile depletion (30-54 hours), bile acid synthesis returned to control levels during 25 mol of cholate and of both deoxycholate doses. In contrast, only 50 mol of cholate prevented derepression of bile acid synthesis. This long-term effect was mainly attributed to a diminished formation from de novo cholesterol exceeding the reduced synthesis from preformed cholesterol. In summary, short-and long-term regulation of bile acid synthesis in hamsters differs with respect to availabilities of preformed and de novo cholesterol. (HEPATOL-OGY 1999;30:230-237.)

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Regulation of bile acid synthesis. I. Effects of conjugated ursodeoxycholate and cholate on bile acid synthesis in chronic bile fistula rat

et al. 1988

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Bile acid synthesis is thought to be regulated by a negative feedback mechanism which is presumably dependent upon the flux of bile acids in the enterohepatic circulation. To characterize further the role of bile acids in regulation of bile acid synthesis, we have administered pure taurine or glycine conjugates of ursodeoxycholic acid or cholic acid to chronic bile fistula rats by continuous intraduodenal infusion, thus simulating restoration of the enterohepatic circulation. The effects of these bile salt infusions on bile acid synthesis, biliary cholesterol and phospholipid secretion and on the activities of the hepatic microsomal enzymes cholesterol 7 alpha-hydroxylase and HMG-CoA reductase were evaluated. Because the rate of biliary bile salt secretion in rats with intact exteriorized enterohepatic circulation averaged 27.1 +/- 1.4 mumoles per 100 gm rat per hr, infusion rates for bile fistula studies were chosen to match (24 to 36 mumoles per 100 gm rat per hr) or exceed (48 mumoles per 100 gm rat per hr) this physiological flux. Infusion of tauroursodeoxycholic acid for 48 hr at 24 and 48 mumoles per 100 gm rat per hr failed to suppress cholic acid synthesis. Bile flow and biliary cholesterol and phospholipid secretion exhibited small, dose-dependent increases with tauroursodeoxycholic acid infusions. No suppression of cholesterol 7 alpha-hydroxylase or HMG-CoA reductase activity was observed. By contrast, taurocholic acid inhibited synthesis of chenodeoxycholate and its metabolites alpha- and beta-muricholate by 10% (NS), 66% (p less than 0.05) and 75% (p less than 0.05) at infusion rates of 24, 36 and 48 mumoles per 100 gm rat per hr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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The effect of portal blood bile salt concentrations on bile salt synthesis in rat liver

Cited by 27 publications

References 16 publications

Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.

Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.

Complex feedback regulation of bile acid synthesis in the hamster: The role of newly synthesized cholesterol

Regulation of bile acid synthesis. I. Effects of conjugated ursodeoxycholate and cholate on bile acid synthesis in chronic bile fistula rat

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