Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Hepatocyte apical membrane

It is also important to predict the in vivo biliary excretion clearance in humans, and for this purpose MDCK II cell lines expressing both uptake and efflux transporters may be used (Fig. 12.3) [92, 93]. It has been shown that MRP2 is expressed on the apical membrane, whereas OATP2 and 8 are expressed on the basolateral membrane after cDNA transfection (Fig. 12.3) [92, 93]. The transcellular transport across such double-transfected cells may correspond to the excretion of ligands from blood into bile across hepatocytes. Indeed, the vectorial transport from the basal to apical side was observed for pravastatin only in OATP2- and MRP2-expressing... [Pg.296]

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... [Pg.199]

A more recent example of this technique has been the study on human absorption characteristics of fexofenadine [109], Fexofenadine has been shown to be a substrate for P-gp in the in vitro cell lines its disposition is altered in knockout mice lacking the gene for MDRla, and co-administration of P-gp inhibitors (e.g. ketoconazole and verapamil) was shown to increase the oral bioavailability of fexofenadine [110-113], Hence, it is suggested that the pharmacokinetics of fexofenadine appears to be determined by P-gp activity. In the human model, the intestinal permeability estimated on the basis of disappearance kinetics from the jejunal segment is low, and the fraction absorbed is estimated to be 2% [114], Co-administration of verapamil/ketoconazole did not affect the intestinal permeability estimates however, an increased extent of absorption (determined by de-convolution) was demonstrated. The increased absorption of fexofenadine was not directly related to inhibition of P-gp-mediated efflux at the apical membrane of intestinal cells as intestinal Peff was unchanged. Furthermore, the effect cannot be explained by inhibition of intestinal based metabolism, as fexofenadine is not metabolised to any major extent. It was suggested that this may reflect modulation of efflux transporters in hepatocyte cells, thereby reducing hepatobiliary extraction of fexofenadine. [Pg.61]

Figure 2.2 Secretion of bile acids and biliary components. Bile acids (BA) cross the hepatocyte bound to 3a-hydroxysteroid dehydrogenase and are exported into the canaliculus by the bile-salt export protein (BSEP). Phosphatidylcholine (PC) from the inner leaflet of the apical membrane is flipped to the outer layer and interacts with bile acids secreted by BSEP. BA, PC, together with cholesterol from the membrane form mixed micelles that are not toxic to epithelial membranes of the biliary tree. Aquaporins (AQP) secrete water into bile. Figure 2.2 Secretion of bile acids and biliary components. Bile acids (BA) cross the hepatocyte bound to 3a-hydroxysteroid dehydrogenase and are exported into the canaliculus by the bile-salt export protein (BSEP). Phosphatidylcholine (PC) from the inner leaflet of the apical membrane is flipped to the outer layer and interacts with bile acids secreted by BSEP. BA, PC, together with cholesterol from the membrane form mixed micelles that are not toxic to epithelial membranes of the biliary tree. Aquaporins (AQP) secrete water into bile.
Figure 2.3 Absorption of bile acids by the cholangiocyte in the cholehepatic shunt. Bile acids are absorbed at the apical membrane of the cholangioc5de by the apical sodium-dependent bile-acid transporter (ASBT) that causes cholehepatic shunting of bile acids back to the hepatocyte. Absorbed bile adds are exported across the basolateral membrane by multi-drug-resistance-associated protein 3 (MRP3), a truncated form of ASBT or by the het-eromeric organic solute (OST) a and p forms. Bile adds cause choleresis that is rich in bicarbonate ions secreted by the chloride/bicarbonate ion exchanger. Figure 2.3 Absorption of bile acids by the cholangiocyte in the cholehepatic shunt. Bile acids are absorbed at the apical membrane of the cholangioc5de by the apical sodium-dependent bile-acid transporter (ASBT) that causes cholehepatic shunting of bile acids back to the hepatocyte. Absorbed bile adds are exported across the basolateral membrane by multi-drug-resistance-associated protein 3 (MRP3), a truncated form of ASBT or by the het-eromeric organic solute (OST) a and p forms. Bile adds cause choleresis that is rich in bicarbonate ions secreted by the chloride/bicarbonate ion exchanger.
BCRP is classified in ABCG subfamily other members of this subfamily are involved in sterol transport (269). Unlike P-gp and MRPs, BCRP consists of a single ABC cassette in the amino terminal followed by six putative transmembrane domains however, it forms a homodimer linked by a disulfide bond in the plasma membrane (270,271). Initially, ABCG2 was identified as an mRNA expressed in placenta (272) and as a non-MDRl- and non-MRP-type resistance factor from cell lines selected in the presence of anthracy-clines and mitoxantrone (273). BCRP is expressed widely in the normal tissues (274) and localized on the canalicular membrane of the hepatocytes and apical membranes of epithelial cells (274,275) and brain capillary endothelial cells (276,277). [Pg.167]

Cellular hydration markedly affects epithelial transcellular transport, as exemplified by transcellular bile acid transport in the liver. In the hepatocyte, conjugated bile acids are taken up at the sinusoidal (basolateral) side by an Na+-dependent carrier and are excreted at the canalicular (apical) membrane by means of a specific... [Pg.201]

The preparation of plasma membrane vesicles from liver canalicular membrane is highly enriched with the canalicular (apical) isoform MRP2 (Buchler et al. 1996). Methods for the isolation of hepatocyte canalicular membranes from liver tissue have been described in detail (Bohme et al. 1994 and Boyer and Meier et al. 1990). The percentage of inside-out-oriented vesicles in these preparations amounts to 32%. Alternatively, transfected I ILK and MDCK cells are often used to study ATP-dependent transport into inside-out vesicles (Cui et al. 1999 Leier et al. 2000). [Pg.536]

It has been suggested that multidrug resistance proteins (MRPs) play an important role in the transport and detoxification of a wide range of endogenous compounds and xenobiotics. They are predominantly expressed at the apical membrane of the small intestine, proximal tubules of the kidney and canalicular membrane of hepatocytes involved in intestinal, renal and hepatobiliary excretion of compounds. [Pg.537]

A key feature of the liver is the antidromic blood and bile flow system (Fig. lc). Blood enters the lobules in the periphery, passes the sinusoids, and is drained off into the central vein. Bile is secreted by the hepatocytes into the apical bile canaliculi, which form a network organized parallel as well as perpendicular to the sinusoidal vessels. Bile flows to the bile ducts in the periportal field and is finally drained off into the gall bladder and the small intestine. The bile canalicular network is not composed of conventional vessels with endothelial cells. It is formed by the apical membrane of hepatocytes and thereby is a consequence of the polar structure of these cells which have an apical pole (facing the bile canaliculus) and a basolateral side (facing the sinusoid). The direct contact to bile leads to a high vulnerability of hepatocytes. Destruction of the apical hepatocyte membrane may lead to bile acids entering the cell, hepatocyte killing, and inflammation. [Pg.31]

Interestingly, the distribution of BCRP in normal tissues is similar to that of P-glycoprotein. High levels of BCRP expression were detected in the human placenta syncytiotrophoblast plasma membrane, facing the maternal bloodstream, in the canalicular membrane of the liver hepatocytes, the apical membrane of the epithelium in the small and large intestines, in the ducts and lobules of the breast, and in the luminal surface of brain capillaries.260 261 In addition, significant amounts of... [Pg.395]

The first member of this carrier family, Oatplal, has been cloned from rat liver [8]. Oatplal is an 80 kDa protein that is expressed at the basolateral membrane of hepatocytes as well as at the apical membranes ofthe renal proximal tubular cells and choroid plexus epithelial cells [11-14]. [Pg.93]

For example, some SLC on the sinusoidal (basolateral) membrane of hepatocytes take up organic anions, while the ABC on the apical membranes of bile canicular cells excrete them. The combined activities of these two transporters thus results in the vectorial transport of drugs from the blood to the bile. Similarly, the basolateral transporters of the kidney tubular cells act in a coordinated, vectorial manner with apical transporters to secrete organic cations (OCs) from the blood to the urine. [Pg.700]

In hepatocytes and some other polarized cells, all plasma-membrane proteins are directed first to the basolateral membrane. Apically destined proteins then are endocytosed and moved across the cell to the apical membrane (transc a osis). [Pg.727]

A FIGURE 18-11 Major transport proteins in the liver and intestines taking part in the enterohepatic circulation of biliary lipids. The secretion of bile components and recycling of bile acids are mediated by a diverse array of transport proteins in liver cells (hepatocytes) and intestinal epithelial cells. Both of these polarized cell types import lipids across one surface and export them across the opposite surface. Step D Hepatocytes export lipids across their apical membranes into the bile by using three ATP-dependent ABC proteins ABCB4 (phospholipids), ABCB11 (bile acids), and ABCG5/8 (sterols). Step B. Intestinal epithelial cells import bile components and dietary lipids from the... [Pg.756]

PgP is expressed on the apical membrane of intestinal epithelial cells, the luminal membrane of proximal tubular epithelia, the apical (or bile canalicular) membrane of hepatocytes, and on the luminal membrane of brain capillary endothelial cells. Accordingly, it is situated to play a role in intestinal drug absorption, renal drug excretion, biliary drug excretion, as well... [Pg.315]


See other pages where Hepatocyte apical membrane is mentioned: [Pg.299]    [Pg.342]    [Pg.343]    [Pg.347]    [Pg.389]    [Pg.382]    [Pg.24]    [Pg.27]    [Pg.27]    [Pg.534]    [Pg.130]    [Pg.234]    [Pg.54]    [Pg.54]    [Pg.392]    [Pg.327]    [Pg.379]    [Pg.15]    [Pg.112]    [Pg.113]    [Pg.113]    [Pg.114]    [Pg.115]    [Pg.276]    [Pg.32]    [Pg.33]    [Pg.727]    [Pg.756]    [Pg.178]    [Pg.431]    [Pg.402]    [Pg.225]    [Pg.111]    [Pg.426]   
See also in sourсe #XX -- [ Pg.300 ]




SEARCH



Apical

Apical membrane

Hepatocyte membranes

© 2024 chempedia.info