Transporter-mediated bile acid uptake causes Ca2+-dependent cell death in rat pancreatic acinar cells

Kim, Joo Young; Kim, Kyung Hwan; Lee, Jin Ah; Namkung, W.; Sun, An-Qiang; Ananthanarayanan, M.; Suchy, Frederick J.; Shin, Dong Min; Muallem, Shmuel; Lee, Min Goo

doi:10.1053/gast.2002.33617

Cited by 155 publications

(168 citation statements)

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“…Because more than 80% of the hepatic uptake of taurocholate appears in a sodium-dependent manner and Ntcp-specific antisense oligonucleotides blocked the Na + -dependent taurocholate uptake in rat liver mRNA-injected Xenopus laevis oocytes by 95% , Ntcp represents the predominant taurocholate uptake system in hepatocytes (Trauner and Boyer 2003;Kullak-Ublick et al 2004). More recently, expression of rat Ntcp was also detected in the luminal membrane of pancreatic acinar cells (Kim et al 2002). Under normal physiological conditions, Ntcp may here be involved in the clearance of bile acids that leak to the terminal acini.…”

Section: Functional Properties and Expression Patterns Of The Individmentioning

confidence: 95%

“…Under normal physiological conditions, Ntcp may here be involved in the clearance of bile acids that leak to the terminal acini. However, bile acid uptake into pancreatic acinar cells is also associated with cell injury and pancreatic disorders (Kim et al 2002). NTCP/Ntcp genes are located on chromosomes 14q24, 6q24 and 12 D1 in man, rat and mouse, respectively Cohn et al 1995;Green et al 1998).…”

Section: Functional Properties and Expression Patterns Of The Individmentioning

confidence: 99%

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The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

Geyer

Wilke

Petzinger

2006

Naunyn Schmied Arch Pharmacol

158

138

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The solute carrier family 10 (SLC10) comprises two sodium-dependent bile acid transporters, i.e. the Na + / taurocholate cotransporting polypeptide (NTCP; SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT; SLC10A2). These carriers are essentially involved in the maintenance of the enterohepatic circulation of bile acids mediating the first step of active bile acid transport through the membrane barriers in the liver (NTCP) and intestine (ASBT). Recently, four new members of the SLC10 family were described and referred to as P3 (SLC10A3), P4 (SLC10A4), P5 (SLC10A5) and sodium-dependent organic anion transporter (SOAT; SLC10A6). Experimental data supporting carrier function of P3, P4, and P5 is currently not available. However, as demonstrated for SOAT, not all members of the SLC10 family are bile acid transporters. SOAT specifically transports steroid sulfates such as oestrone-3-sulfate and dehydroepiandrosterone sulfate in a sodium-dependent manner, and is considered to play an important role for the cellular delivery of these prohormones in testes, placenta, adrenal gland and probably other peripheral tissues. ASBT and SOAT are the most homologous members of the SLC10 family, with high sequence similarity (∼70%) and almost identical gene structures. Phylogenetic analyses of the SLC10 family revealed that ASBT and SOAT genes emerged from a common ancestor gene. Structure-activity relationships of NTCP, ASBT and SOAT are discussed at the amino acid sequence level.Based on the high structural homology between ASBT and SOAT, pharmacological inhibitors of the ASBT, which are currently being tested in clinical trials for cholesterollowering therapy, should be evaluated for their crossreactivity with SOAT.

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Section: Functional Properties and Expression Patterns Of The Individmentioning

confidence: 95%

Section: Functional Properties and Expression Patterns Of The Individmentioning

confidence: 99%

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

Geyer

Wilke

Petzinger

2006

Naunyn Schmied Arch Pharmacol

158

138

View full text Add to dashboard Cite

show abstract

“…Administration of submillimolar concentrations of chenodeoxycholic acid (CDC) 3 to the lumen of ex vivo ducts elicits reactive mechanisms within the pancreatic duct cell to stimulate bicarbonate secretion (10,11). However, higher concentrations of CDC induce acinar cell pathology, leading to pancreatitis (12,13).…”

mentioning

confidence: 99%

Bile Acids Induce Pancreatic Acinar Cell Injury and Pancreatitis by Activating Calcineurin

Muili

Wang

Orabi

et al. 2013

Journal of Biological Chemistry

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“…In case of coexisting cholelithiasis, bacteria colonizing gall-bladder and bile ducts are the fi rst element. Bile acids are the second potential factor, as their damaging infl uence on epithelium of bile ducts and pancreatic ducts, as well as pancreatic follicular cells was confi rmed by experimental works (11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 93%

“…Calcium ions seem to play a key role within these phenomena. Small concentrations of bile acids activate intracellular "calcium-dependent" signals, resulting in uncontrolled activa-tion of zymogen and induction of infl ammatory process within the cellular level (14,15,16,30).…”

mentioning

confidence: 99%

Bile Infection and Bile Acids Concentration in Bile in Acute Biliary Pancreatitis

Zasada¹,

Panek²,

Dolecki³

et al. 2009

Polish Journal of Surgery

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Biliary stones are the most common etiology of acute pancretitis (AP). Pathomechanism of this etiology is based on common channel theory of Opie. Material and methods. 113 patients with ABP were included in the study -91 with mild and 22 with severe form of ABP. 17 patients with cholelithiasis and choledocholithiasis without ABP served as controls. All the patients were submitted to the same model of treatment. Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sfi ncterotomy (ES) were performed in the day of admission and laparoscopic cholecystectomy within the next 24 hours. Bile specimens were taken from main bile duct (MBD) during ERCP and from gall-bladder (GB) during laparoscopic cholecystectomy. Bacteriological cultures, bile acids (BA) concentration and total and secretory form of IgA concentration were assessed in particular groups of patients. Results. No signifi cant statistical differences of bile infection in MBD and GB were found between the analyzed groups of patients. Furthermore, the bile among the patients with severe ABP was more frequently infected, particularly when obtained from gall-bladder. Most common pathogens found in cultures were Gram negative bacteria. Interestingly, Gram positive cultures and fungi were also signifi cant. The number of species of pathogens was of no signifi cance for infection concerning both: source of bile and groups of patients. Mean concentrations of total BA were different between study groups of patients in MBD and in GB. It is worth mentioning, that the fraction of hydrophobic, secondary BA which are potentially more toxic, was increased in total concentration of BA in MBD particularly in patients with severe form of AP. Among patients with mild AP and controls these values were lower and similar. Conclusions. It seems that BA play as an aggressive factor during AP while in physiologic condition have a protective, antibacterial meaning.

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Transporter-mediated bile acid uptake causes Ca2+-dependent cell death in rat pancreatic acinar cells

Cited by 155 publications

References 36 publications

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

Bile Acids Induce Pancreatic Acinar Cell Injury and Pancreatitis by Activating Calcineurin

Bile Infection and Bile Acids Concentration in Bile in Acute Biliary Pancreatitis

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