P-Glycoprotein and Bilirubin Disposition

Watchko, Jon F.; Daood, Monica J.; Mahmood, Burhan; Vats, Kalyani; Hart, Claudia; Ahdab-Barmada, Mamdouha

doi:10.1038/sj.jp.7210633

Cited by 41 publications

(33 citation statements)

References 18 publications

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“…The production rates of UCB in the organ and the permeability to UCB of the blood-organ barriers (10) determine the supply of UCB. Because Gunn (jj) rats cannot conjugate bilirubin, the cellular export of UCB (15,16,18,19) and UCB oxidation (12,14,(26)(27)(28) might play a role in UCB removal from the brain of these animals.…”

Section: Discussionmentioning

confidence: 99%

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Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups

et al. 2012

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Section: Discussionmentioning

confidence: 99%

“…Export of UCB by two ATP-binding cassette transporters (ABCc1 and ABCb1) has a role in protecting cultured central nervous system cells from UCB toxicity (15)(16)(17)(18)(19). Therefore, the mRNA expression of the three Cyps and two ABC transporters was assessed in selected brain regions by quantitative PCR (qPCR).…”

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confidence: 99%

Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups

et al. 2012

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“…Its unusual promiscuity has made it hard to find compounds that are not substrates. Accordingly, ABCB1 has been implicated in the transport of various endogenous compounds, such as cholesterol (Lee et al, 2013) (Jetté et al, 1995;Watchko et al, 2001), and tetrahydroxylated bile acids (Megaraj et al, 2010). Most of these compounds were only investigated in vitro and/or showed a low affinity for ABCB1.…”

Section: Abcb1mentioning

confidence: 99%

The Role of Canalicular ABC Transporters in Cholestasis

et al. 2014

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Cholestasis, a hallmark feature of hepatobiliary disease, is characterized by the retention of biliary constituents. Some of these constituents, such as bile acids, inflict damage to hepatocytes and bile duct cells. This damage may lead to inflammation, fibrosis, cirrhosis, and eventually carcinogenesis, sequelae that aggravate the underlying disease and deteriorate clinical outcome. Canalicular ATP-binding cassette (ABC) transporters, which mediate the excretion of individual bile constituents, play a key role in bile formation and cholestasis. The study of these transporters and their regulatory nuclear receptors has revolutionized our understanding of cholestatic disease. This knowledge has served as a template to develop novel treatment strategies, some of which are currently already undergoing phase III clinical trials. In this review we aim to provide an overview of the structure, function, and regulation of canalicular ABC transporters. In addition, we will focus on the role of these transporters in the pathogenesis and treatment of cholestatic bile duct and liver diseases.

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“…P-gp is normally expressed in endothelial or epithelial cells of several organs including the brain, liver, intestine, and kidney (Gottesman and Pastan, 1993). Evidence supports a role for the P-gp transporter in the disposition or elimination of endogenous substances including corticosteroids, estrogens, and bilirubin (Karssen et al, 2001;Watchko et al, 2001;Kim and Benet, 2004). This transporter also plays a key role in the disposition and excretion of a wide array of clinically used drugs and provides protection against the accumulation of toxic xenobiotics within tissues (Schinkel et al, 1994;Mayer et al, 1996;Johnson et al, 2001).…”

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confidence: 99%