Canalicular bile formation in the isolated perfused rat liver

Jl, Boyer

doi:10.1152/ajplegacy.1971.221.4.1156

Cited by 121 publications

(60 citation statements)

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“…According to the current concept, bile flow is regulated by bile salt-dependent (33) and -independent mechanisms (34) and the increase of biliary bile acids is expected to increase the bile flow. however, there was no increase in bile flow in the present experiments.…”

Section: Resultsmentioning

confidence: 99%

Altered Bile Acid Metabolism in Alloxan Diabetic Rats

Uchida

Takase

Kadowaki

et al. 1979

Japanese Journal of Pharmacology

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Abstract-Changes of cholesterol, phospholipid, triglyceride or bile acid levels in serum, liver, bile and feces after the treatment with alloxan were examined in Wistar strain male rats. Serum cholesterol, phospholipid and triglyceride levels and liver cholesterol level markedly increased but liver phospholipid and triglyceride levels remained un changed. The lipid levels in serum very low density and low density lipoproteins were elevated but those in high density lipoprotein were not. Bile flow was not changed but biliary secretion of cholesterol, phospholipid and bile acids markedly increased. Among the biliary bile acid components, cholic acid markedly increased but the amount of chenodeoxycholic acid was similar to that of normal rats. Fecal excretion of deoxy cholic acid increased but that of lithocholic and hyodeoxycholic acids decreased, and a-, Q and oi-muricholic acids did not change, thus, the total amount of fecal bile acids remained unchanged.Hepatic cholesterol synthesis was markedly depressed, while cholesterol 7a-hydroxylase activity did not change and cytochrome P-450 content was elevated by about 40 %. From such evidence, it was apparent that synthesis of cholic acid increased while that of chenodeoxycholic acid decreased and the total amount of bile acids synthesized did not change in the diabetic rats. Furthermore, marked increase of the pool size of cholic acid and hepatic secretion of cholic acid stimulated the absorption of lipids and produced a hyperlipidemia in the diabetic rats.Serum cholesterol and triglyceride levels in diabetics increase markedly and this increase is related to a high incidence of atherosclerosis (1, 2) and cholesterol gallstones (3). Diabetic rats, treated with alloxan or streptozotocin, also developed marked hyperlipidemia (4-10) with a higher incidence of cardiovascular lesions when fed a high cholesterol diet (7). The mechanism by which marked hyperlipidemia is produced in diabetic rats is not fully under stood, but Bierman et al. (6) have postulated that the intake of dietary fat is related to the manifestration of hyperlipidemia, and Nervi et al. (9) found an increase in biliary secretion and daily synthesis of bile acids in alloxan diabetic rats and concluded that hypercholester olemia is due to an increase in cholesterol absorption. We examined cholesterol or bile acid level in serum, liver, bile and feces of alloxan diabetic rats in an attempt to elucidate the mechanism underlying hypercholesterolemia. MATERIALS AND METHODSMale Wistar rats weighing approximately 300 g were kept in an air-conditioned room (25 --1 °C, 50-60% humidity) lighted 12 hr a day (08:00 to 20:00) and maintained on a com

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Section: Resultsmentioning

confidence: 99%

Altered Bile Acid Metabolism in Alloxan Diabetic Rats

Uchida

Takase

Kadowaki

et al. 1979

Japanese Journal of Pharmacology

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“…The average 02 consumption was 1.73+0.03 ,mol O2/min per g wet liver (mean+SEM). The 02 consumption was -80% of that reported for isolated perfused rat liver studies employing hemoglobin as an 02 carrier (29,34). Glucose synthesis by the perfused liver was determined by examining the production of glucose from lactate.…”

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confidence: 95%

Protoporphyrin-induced Cholestasis in the Isolated In Situ Perfused Rat Liver

Avner¹,

Lee²,

Berenson³

1981

J. Clin. Invest.

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A B S T R A C T The pathogenesis of liver disease in protoporphyria has been presumed to result from the hepatic deposition of protoporphyrin. To examine the effects of protoporphyrin on hepatic bile flow and histopathology, studies were performed employing an isolated, in situ, rat liver perfusion system. Rat livers in the control group were perfused with 0-80 umol sodium taurocholate/h. Rat livers in the experimental group were perfused with sodium taurocholate and (a) sufficient quantities of protoporphyrin to produce maximal canalicular secretion and (b) perfusate protoporphyrin concentrations of 0.01, 0.1, and 1 ,tM.The administration of protoporphyrin sufficient to achieve maximal canalicular secretion was found to significantly reduce bile flow in rats infused with 0, 40, and 80 ,imol sodium taurocholate/h. Linear regression analysis defined the relationship between bile flow and biliary bile acid secretion and showed that the bile acid-independent fraction ofbile flow was reduced (P < 0.01). Bile acid-dependent flow was unaffected and there was no significant difference in biliary bile acid secretion rates between control and protoporphyrin-perfused livers. Perfusion of rat livers with varying concentrations of protoporphyrin demonstrated the reduction of bile flow was dose-related. Analysis of perfusate enzyme activity did not reveal abnormalities that could account for the cholestasis. Studies to evaluate the effect of protoporphyrin on regional hepatic hemodynamics were inconclusive.Histopathological studies of control and protoporphyrin-perfused rat livers did not show ab-

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“…Studies of membrane structure and function both in vivo and in vitro suggest that alterations in lipid composition may alter Na+,K+-ATPase function and bile flow. Na+,K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) is a mammalian surface membrane that is sensitive to the lipid structure of the membrane bilayer (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)). An important function of Na+,K+-ATPase in the hepatocyte may be the active secretion of sodium into the bile canaliculus, thus driving water across the canalicular membrane (8,9).…”

Section: Introductionmentioning

confidence: 99%

“…Na+,K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) is a mammalian surface membrane that is sensitive to the lipid structure of the membrane bilayer (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). An important function of Na+,K+-ATPase in the hepatocyte may be the active secretion of sodium into the bile canaliculus, thus driving water across the canalicular membrane (8,9). This fraction has been called bile salt-independent bile flow, and recent studies have demonstrated a strong correlation between hepatic Na+, K+-ATPase activity and bile flow (10), supporting the hypothesis that this component of bile flow is regulated by the sodium pump.…”

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confidence: 99%

“…Microsomal fractions were prepared from the supernate of the liver surface membrane nuclear pellet by a modification of the procedure of Evans and Gurd (20), previously described (21 Na+,K+-ATPase activity was determined in liver surface membrane fractions and homogenates according to the method of Ismail-Beigi and Edelman with minor modifications (12,23). A detailed account of the procedure used has been reported (9). Under the conditions used hepatic Na+,K+-ATPase activity is linear to protein concentrations of 500 ,ug and for 7.5 min.…”

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Alterations of hepatic Na ⁺ ,K ⁺ -ATPase and bile flow by estrogen: Effects on liver surface membrane lipid structure and function

Davis

Kern

Showalter

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

169

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Administration of the synthetic estrogen ethinyl estradiol (17a-ethinyl-1,3,5-estratriene-3,173diol) decreases hepatic Na+,K+-ATPase (ATP phosphohydrolase; EC 3.6.1.3) activity and bile flow to 50% and alters the composition and structure of surface membrane lipid in rats. Although the content of phospholipids was not changed by treatment, free cholesterol (130%) and cholesterol esters (400%) were increased in liver surface membrane fractions. These observations correlate with changes in membrane viscosity, as shown by electron spin resonance probes. Both rotational correlation time, using the isotropic probe methyl (12-nitroxyl)stearate, and the order parameter, determined by the anisotropic probe 5-nitroxylstearic acid, were significantly increased in liver surface membrane fractions from rats treated with ethinyl estradiol. Administration of Triton WR-1339, a nonionic detergent that corrects hepatic and serum lipid changes caused by ethinyl estradiol treatment, restored toward normal elevated membrane lipids and viscosity as well as Na+,K+-ATPase activity and bile flow. Although restoration of normal liver surface membrane structure and function may be due to reversal of abnormal lipid composition, detergents also may directly alter membrane enzyme activity. Addition of Triton WR-1339 in vitro increased Na+,K+-ATPase activity and reduced membrane viscosity of surface membranes from rats treated with ethinyl estradiol. Triton had no effect on either parameter in normal membrane preparations. Studies of membrane structure and function both in vivo and in vitro suggest that alterations in lipid composition may alter Na+,K+-ATPase function and bile flow. Na+,K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) is a mammalian surface membrane that is sensitive to the lipid structure of the membrane bilayer (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)). An important function of Na+,K+-ATPase in the hepatocyte may be the active secretion of sodium into the bile canaliculus, thus driving water across the canalicular membrane (8,9). This fraction has been called bile salt-independent bile flow, and recent studies have demonstrated a strong correlation between hepatic Na+, K+-ATPase activity and bile flow (10), supporting the hypothesis that this component of bile flow is regulated by the sodium pump. One drug consistently shown to reduce bile salt-independent bile flow is the synthetic estrogen derivative ethinyl estradiol (17a-ethinyl-1,3,5-estratriene-3,17f3-diol) (10)(11)(12)(13).The aim of the present study was to examine whether Na+, K+-ATPase activity is reduced after ethinyl estradiol treatment and, if so, what possible mechanisms might be involved. We recently found that ethinyl estradiol significantly increases hepatic cholesterol ester concentrations by activating hepatic microsomal cholesterol acyl-CoA transferase (14).The possibility that altered membrane lipid composition was involved in the mechanism through which ethinyl estradiolThe publication costs of this article were defrayed in part by page charge payment. Thi...

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Canalicular bile formation in the isolated perfused rat liver

Cited by 121 publications

References 0 publications

Altered Bile Acid Metabolism in Alloxan Diabetic Rats

Altered Bile Acid Metabolism in Alloxan Diabetic Rats

Protoporphyrin-induced Cholestasis in the Isolated In Situ Perfused Rat Liver

Alterations of hepatic Na ⁺ ,K ⁺ -ATPase and bile flow by estrogen: Effects on liver surface membrane lipid structure and function

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Canalicular bile formation in the isolated perfused rat liver

Cited by 121 publications

References 0 publications

Altered Bile Acid Metabolism in Alloxan Diabetic Rats

Altered Bile Acid Metabolism in Alloxan Diabetic Rats

Protoporphyrin-induced Cholestasis in the Isolated In Situ Perfused Rat Liver

Alterations of hepatic Na + ,K + -ATPase and bile flow by estrogen: Effects on liver surface membrane lipid structure and function

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Alterations of hepatic Na ⁺ ,K ⁺ -ATPase and bile flow by estrogen: Effects on liver surface membrane lipid structure and function