Transport systems of isolated hepatocytes

Schwenk, Michael

doi:10.1007/bf00303188

Cited by 48 publications

(1 citation statement)

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“…In initial experiments, samples were obtained at 90 and 300 sec to establish accurate data regarding the time course of uptake. Hepatocytes were immediately separated from the incubation medium by microfuge centrifugation (10,000 X g for 5 sec) through a layer of silicone oil (100 p1) into 3 M KOH (50 p1) (3,35,36,37). After dissolution of the cell pellet in the KOH (18-24 h), the bottom of each microfuge tube was cut off at the silicone oil-KOH interface and placed in a scintillation vial.…”

Section: Speculationmentioning

confidence: 99%

Uptake of Taurocholate by Hepatocytes Isolated from Developing Rats

Suchy

Balistreri

1982

Pediatr Res

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Summaryon Purina rat chow and water ad libitum. Male rats were utilizedTo further define developmental changes in bile acid metabolism, we determined the kinetics of taurocholate uptake by hepatocytes isolated from Sprague-Dawley rats at 7, 14,21,28, and 56 days of age. There was a progressive increase in taurocholate uptake with age. The uptake process exhibited saturable kinetics in every age group with a maximum uptake velocity attained above a taurocholate concentration of 200 pM. There were no differences in Km values but Vmax increased progressively between 7 and 56 days of age. These data suggest that the deficit in hepatic excretory function observed in immature mammals of several species may, in part, be related to decreased transport of bile acids. SpeculationImpaired transport of bile acids by the liver may limit bile flow during development and lead to inefficient fat digestion, altered hepatic excretion of drugs, and an increased susceptibility to cholestasis. Comparable Km values for the uptake process indicate that hepatocyte affinity for taurocholate remains constant during development; whereas the rise in Vmax with postnatal age may reflect an increase in the number of binding sites. Specific changes in the liver cell plasma membrane are likely to be important determinants of the ontogeny of bile acid transport and bile flow.Bile acids are major synthetic and excretory products of the liver and are of primary importance in the generation of bile flow (1 1, 15, 20). There is increasing evidence in humans and in experimental animals that the enterohepatic circulation of bile acids is not fully developed at birth and that the perinatal liver is normally subject to a period of "physiological cholestasis" (13,14,41). In the normal human infant and in the suckling rat, bile acid pool size is decreased (42, 44) and the concentration of bile acids in serum is elevated (5, 6, 41). As a consequence of decreased bile secretion, biliary elimination of many drugs and organic anions such as bilirubin may be impaired (30,43,46) and the concentrations of bile acids reaching the intestine may be inadequate for optimal fat digestion (45). This immaturity of liver function may also place the infant at increased risk for clinical cholestasis as is commonly observed during gram negative infection or during parenteral nutrition (2,8,18). It is our hypothesis that during development, efficient enterohepatic cycling of bile acids may, in part, be limited by immaturity of bile acid transport by the liver. We, therefore, sought maturational changes in the uptake of taurocholate by hepatocytes isolated from suckling and weanling rats.for hepatocyte isolation and all studies were conducted at midday.The chemicals used in this study were: tauro-[~arbonyl-'~C] cholic acid, (52.0 mCi/mmoles; greater than 98% pure by thin layer chromatography) and [3H]-inulin, (1 mCi/6.9 mg) both from New England Nuclear Corp. (Boston, MA); collagenase (type II), Sigma Chemical Corp. (St. Louis, MO); sodium taurocholate (greater than 98% pure ...

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Section: Speculationmentioning

confidence: 99%