Ampicillin inhibits the movements of biliary secretory vesicles in rat hepatocytes

Bellringer, Maria; Steele, Nicholas J.; Rahman, Kahlid; Coleman, Roger

doi:10.1016/0005-2736(88)90215-5

Cited by 24 publications

(17 citation statements)

References 26 publications

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“…All these molecules are transported to the canalicular membrane via vesicle-mediated transport; thus it has been proposed that valproic acid may inhibit the movement of secretory vesicles within the hepatocytes through a mechanism that still needs to be fully elucidated. Similar effects have been reported for ampicillin (Bellringer et al, 1988b).…”

Section: Discussionsupporting

confidence: 87%

“…Numerous compounds are also known to dissociate the biliary secretion of cholesterol and phospholipid from that of bile acids. Examples of these are ampicillin (Apstein & Russo, 1985;Bellringer et al, 1988b), cefoperazone (Pattinson et al, 1987), ceftriaxone (Xia et al, 1990), iodipamide (Apstein & Robbins, 1982), valproic acid (Bellringer et al, 1988a), sulphobromophthalein (Shaffer & Preshaw, 1981), bilirubin (Apstein, 1984) or cyclobutyrol .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of biliary cholesterol and phospholipid secretion by cefmetazole. The role of vesicular transport and of canalicular events

Cava

González

González-Buitrago

et al. 1991

Biochemical Journal

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A number of organic anions selectively inhibit the biliary secretion of cholesterol and phospholipids without affecting bile acid secretion. We studied the effect of cefmetazole, a third-generation cephalosporin, on biliary lipid secretion in the rat. Injection of cefmetazole at a dose of 200,mol/kg body wt. induced a choleretic effect and a significant decrease in the biliary output of cholesterol and phospholipid, without changes in bile acid secretion. The decrease was more marked for cholesterol than for phospholipid secretion, with a significant decrease in their molar ratio in bile. The effects were apparently unrelated to an inhibition of intracellular vesicular transport because, after injection of horseradish peroxidase, both the time course and total amount secreted of the protein did not significantly differ between control animals and those receiving cefmetazole. The secretory rate of the lysosomal marker acid phosphatase was not affected by cefmetazole administration. Biliary outputs of the plasma-membrane enzymes alkaline phosphatase and y-glutamyltransferase were significantly decreased by the antibiotic. These results point to an effect of cefmetazole at the level of the canalicular membrane.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Inhibition of biliary cholesterol and phospholipid secretion by cefmetazole. The role of vesicular transport and of canalicular events

Cava

González

González-Buitrago

et al. 1991

Biochemical Journal

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“…An insight into the possible intracellular mechanism for biliary lipid interaction is provided by studies showing that administration of substances such as colchicine and vinblastine, both known to inhibit microtubular function and hence vesicle movement inside the hepatocyte, reduce cholesterol and phospholipid secretion [65-671. A similar effect is observed by exposing the liver to ampicillin and valproic acid [68,69], substances known to inhibit vesicular transport of IgA and albumin from the sinusoidal to the canalicular pole of the hepatocyte. These observations suggest that a vesicular transport system is involved in cholesterol and phospholipid secretion.…”

Section: Biliary Lipid Couplingmentioning

confidence: 53%

Biliary lipid secretion in man

Lanzini

Northfield

1991

Eur J Clin Investigation

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“…Studies with different species have shown that cholesterol and phospholipid biliary outputs increase in proportion to the increases in biliary bile acid secretion brought about by bile acid loads, 33,34 suggesting that biliary lipid secretion is tightly coupled to biliary secretion of bile acids. However, some organic anions, such as bilirubin, 12 certain antibiotics 13,35 , 36 and bile acid sulphates 37,38 have been reported to decrease cholesterol and phospholipid biliary excretion without affecting bile acid secretion. This uncoupling effect could be a consequence, as reported for ampicillin and bilirubin ditaurate, of aggregate formation with intracellular cholesterol and phospholipids, thereby inhibiting lipid transport from intracellular sources to bile 12,13 .…”

Section: Discussionmentioning

confidence: 99%

Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat

González

Mauriz

Jiménez

et al. 2002

Clin Exp Pharma Physio

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1. The effects of the administration piperacillin on bile flow and biliary lipid secretion were studied in male Wistar rats. 2. Intravenous injection of piperacillin at doses ranging from 0.3 to 3.0 mmol/kg bodyweight led to an increase in its biliary concentration and excretion rate. Maximal biliary excretion was reached at a dose of 2.0 mmol/kg piperacillin. 3. Excretion of the antibiotic into bile was associated with a marked choleresis. A linear relationship was observed between bile flow and piperacillin excretion, 5.7 micro L bile being produced per micro mol piperacillin excreted into the bile. 4. Continuous i.v. infusion of piperacillin at 2.0 mmol/100 g per min did not result in significant changes in bile acid or cholesterol secretion, but biliary phospholipid secretion was markedly reduced. The inhibitory effect on phospholipid secretion was also present when biliary lipid output had been previously increased by an infusion of taurocholate (200 nmol/100 g per min). Addition of taurocholate did not reverse the impairment of phospholipid secretion induced by piperacillin. 5. These results indicate that acute administration of piperacillin in the rat induces a marked choleresis by stimulating bile acid-independent bile flow. The significant impairment in phospholipid secretion suggests a specific effect on intracellular supply and/or translocation across the canalicular membrane.

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Ampicillin inhibits the movements of biliary secretory vesicles in rat hepatocytes

Cited by 24 publications

References 26 publications

Inhibition of biliary cholesterol and phospholipid secretion by cefmetazole. The role of vesicular transport and of canalicular events

Inhibition of biliary cholesterol and phospholipid secretion by cefmetazole. The role of vesicular transport and of canalicular events

Biliary lipid secretion in man

Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat

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