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B Noé

Publications and source records attributed to B Noé.

5 recordsLinked to original sources
PubMed1999

Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain.

In this study we investigated the distribution of a recently cloned polyspecific organic anion transporting polypeptide (Oatp2) in rat brain by nonradioactive in situ hybridization histochemistry and immunofluorescence microscopy. The results demonstrate that Oatp2 is expressed in brain capillary and in plexus epithelial cells. At the blood-brain barrier (BBB), Oatp2 expression could be co-localized with the endothelial marker vWF (von Willebrand factor) but not with the astrocyte marker GFAP (glial fibrillary acidic protein). In choroid plexus epithelial cells, Oatp2 could be localized to the basolateral cell pole, whereas the first member of the Oatp gene family of membrane transporters to be cloned (Oatp1) co-localized with the alpha(1)-subunit of Na,K-ATPase at the apical plasma membrane domain. Because Oatp1 and Oatp2 have been previously shown to mediate transmembrane transport of a wide variety of amphipathic organic compounds, including many drugs and other xenobiotics, the histochemical localization of Oatp2 at the BBB and of Oatp1 and Oatp2 in the choroid plexus imply a role for these transporters in the active exchange of amphipathic solutes between the blood, brain, and cerebrospinal fluid compartments. (J Histochem Cytochem 47:1255-1263, 1999)

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PubMed1997

Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain.

A novel multispecific organic anion transporting polypeptide (oatp2) has been isolated from rat brain. The cloned cDNA contains 3,640 bp. The coding region extends over 1,983 nucleotides, thus encoding a polypeptide of 661 amino acids. Oatp2 is homologous to other members of the oatp gene family of membrane transporters with 12 predicted transmembrane domains, five potential glycosylation, and six potential protein kinase C phosphorylation sites. In functional expression studies in Xenopus laevis oocytes, oatp2 mediated uptake of the bile acids taurocholate (Km approximately 35 microM) and cholate (Km approximately 46 microM), the estrogen conjugates 17beta-estradiol-glucuronide (Km approximately 3 microM) and estrone-3-sulfate (Km approximately 11 microM), and the cardiac gylcosides ouabain (Km approximately 470 microM) and digoxin (Km approximately 0.24 microM). Although most of the tested compounds are common substrates of several oatp-related transporters, high-affinity uptake of digoxin is a unique feature of the newly cloned oatp2. On the basis of Northern blot analysis under high-stringency conditions, oatp2 is highly expressed in brain, liver, and kidney but not in heart, spleen, lung, skeletal muscle, and testes. These results provide further support for the overall significance of oatps as a new family of multispecific organic anion transporters. They indicate that oatp2 may play an especially important role in the brain accumulation and toxicity of digoxin and in the hepatobiliary and renal excretion of cardiac glycosides from the body.

Amino Acid Sequence↗
PubMed1996

Regulation of taurocholate excretion by a hypo-osmolarity-activated signal transduction pathway in rat liver.

BACKGROUND & AIMS: Hypo-osmotic cell swelling increases the capacity of taurocholate excretion into bile in the perfused rat liver. The aim of this study was to clarify the mechanisms linking cell swelling to bile acid secretion. METHODS: The influence of hypo-osmotic cell swelling on intracellular signal transduction and bile acid secretion was studied in isolated rat hepatocytes and the perfused rat liver. RESULTS: In rat livers perfused with hypo-osmotic buffer (225 mOsm/L), the maximum velocity of taurocholate excretion into bile is increased by 135% within 10-20 minutes. To unravel signaling events mediating this effect, the activities of the mitogen-activated protein kinases, extracellular-signal-regulated kinase (Erk)-1 and Erk-2, were measured after hypo-osmotic treatment in cultured rat hepatocytes. A rapid parallel activation of Erk-1 and Erk-2 was observed within 1 minute, which became maximal after 10 minutes and returned to the basal level within 60 minutes. The hypo-osmolarity-induced Erk activation and the increase in bile flow after hypo-osmotic liver perfusion were completely abolished by inhibitors of signal transduction at the level of G proteins and tyrosine kinases but remained unaffected by the inhibition of the protein kinase C. CONCLUSIONS: A G protein-and tyrosine kinase-dependent but protein kinase C-independent activation of mitogen-activated protein kinases is involved in the regulation of taurocholate excretion by liver cell hydration changes.

Animals↗
PubMed1995

Metabolism of cysteinyl leukotrienes in the perfused rat liver: the influence of endotoxin pretreatment and the cellular hydration state.

The influence of endotoxin on the hepatic metabolism and elimination of 3H-leukotriene C4 (LTC4) and 3H-leukotriene E4 was studied in the single-pass perfused rat liver. Endotoxin (4 mg/kg body mass) was injected intraperitoneally 8 to 10 hours before livers were isolated for perfusion. Tritiated leukotriene C4 and leukotriene E4 (10 nmol/L) were infused for 5 minutes, and metabolites in bile were determined by high-pressure liquid chromatography. In livers without endotoxin pretreatment, single-pass uptake of LTC4 was 77.3% +/- 3.2%, and 73.8% +/- 1.8% of the radioactivity taken up was excreted into the bile within 80 minutes. In endotoxin-pretreated livers, LTC4 uptake was 62.8% +/- 3.5% and only 31.2% +/- 1.5% of the radioactivity taken up was eliminated into the bile within 80 minutes. Bile flow was reduced to 0.20 +/- 0.07 microL/min, compared with 1.18 +/- 0.18 microL/g/min in untreated livers. Biliary excretion of infused 3H-LTE4 was also reduced in endotoxin-pretreated livers (31.5% +/- 6.1% compared with 61.4% +/- 3.3% without endotoxin pretreatment), whereas uptake was not significantly different. The effect of cellular hydration state on leukotriene processing was also investigated. Anisoosmotic cell volume changes did not influence uptake and biliary excretion of 3H-LTC4 and its metabolism in control livers. In endotoxin-pretreated livers, however, cell swelling induced by hypotonic perfusion media (225 mOsm/L) or by 3 mmol/L glutamine increased biliary elimination of the radioactivity taken up by 68% and 54%, respectively. Bile flow was also stimulated (0.31 +/- 0.09 microL/g/min and 0.46 +/- 0.01 microL/g/min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

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