ABCC3 p.Gly1316Ala
| Predicted by SNAP2: | A: N (61%), C: N (57%), D: D (80%), E: N (53%), F: D (71%), H: N (57%), I: D (71%), K: N (61%), L: D (75%), M: N (78%), N: N (78%), P: D (80%), Q: N (78%), R: N (72%), S: N (82%), T: N (78%), V: D (71%), W: D (80%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Involvement of multidrug resistance-associated pro... Drug Metab Dispos. 2008 Jun;36(6):1088-96. Epub 2008 Mar 13. Kato Y, Takahara S, Kato S, Kubo Y, Sai Y, Tamai I, Yabuuchi H, Tsuji A
Involvement of multidrug resistance-associated protein 2 (Abcc2) in molecular weight-dependent biliary excretion of beta-lactam antibiotics.
Drug Metab Dispos. 2008 Jun;36(6):1088-96. Epub 2008 Mar 13., [PMID:18339814]
Abstract [show]
In the present study, we attempted to identify the membrane permeation process(es) primarily involved in the molecular-weight-dependent biliary excretion of beta-lactam antibiotics. A search of the literature indicated that the molecular weight threshold operates mainly in the transport process across bile canalicular membranes. We confirmed that biliary clearance of the model biliary-excretion-type cephalosporin cefoperazone was reduced to 10% of the control in Eisai hyperbilirubinemic rats, which are genetically deficient in multidrug resistance-associated protein (Mrp) 2, indicating that Mrp2 plays a major role as an efflux transporter on the canalicular membranes. ATP-dependent uptake of several cephalosporins including cefoperazone, cefbuperazone, cefpiramide, and ceftriaxone, all of which are mainly excreted into bile, was confirmed in membrane vesicles from Sf9 cells transfected with rat Mrp2. Both the inhibitory potency of the cephalosporins for Mrp2-mediated transport and the uptake of cephalosporins by Mrp2-expressing vesicles were molecular weight-dependent, suggesting that Mrp2 is one of the major transporters involved in molecular weight-dependent biliary excretion. An uptake study in membrane vesicles of Sf9 cells transfected with breast cancer resistance protein (Bcrp) revealed that Bcrp accepts cefoperazone, cefbuperazone, cefpiramide, cefotetan, ceftriaxone, cefotiam, cefamandole, and cefazolin as substrates, and Bcrp-mediated transport was also molecular weight-dependent, suggesting that Bcrp also contributes to molecular weight-dependent biliary excretion of beta-lactam antibiotics in rats.
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82 The concentration of cephalosporin was measured by with a LC-tandem mass spectrometry system equipped with a constant flow pump (1200 series G1312A; Agilent Technologies, Tokyo, Japan), an automatic sample injector (G1367B; Agilent Technologies), a column oven (G1316A; Agilent Technologies), and a tandem mass spectrometer (API 3200; Applied Biosystems, Tokyo, Japan).
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ABCC3 p.Gly1316Ala 18339814:82:262
status: NEW[hide] Membrane transport of nobilin conjugation products... Eur J Pharm Sci. 2015 Apr 5;70:92-106. doi: 10.1016/j.ejps.2014.11.011. Epub 2014 Dec 2. Thormann U, Hanggi R, Kreuter M, Imanidis G
Membrane transport of nobilin conjugation products and use of the extract of Chamomillae romanae flos influence absorption of nobilin in the Caco-2 model.
Eur J Pharm Sci. 2015 Apr 5;70:92-106. doi: 10.1016/j.ejps.2014.11.011. Epub 2014 Dec 2., [PMID:25477003]
Abstract [show]
The purpose of this work was to investigate the role of bioconjugation and carrier mediated efflux of conjugation products in the absorption mechanism of the sesquiterpene lactone nobilin in the Caco-2 model in vitro and to elucidate the impact of the extract of Chamomillae romanae flos and its ingredients on absorption. Transport experiments with inhibitors of P-gp, BCRP, and MRPs were performed to detect efflux and its connection to bioconversion and the effect of different ingredients of the plant extract on absorption processes was determined. Permeability, transport and bioconversion parameter values were deduced by kinetic multi-compartment modeling. Nobilin exhibited high permeability, low relative absorption and fast bioconversion producing glucuronide, cysteine conjugate, and glutathione conjugate that were transported by P-gp (the first two), apical MRP2 and basal MRP3 and possibly MRP1 out of the cell. Inhibition of efflux resulted in diminished bioconjugation and improved absorption. The extract increased the relative fraction absorbed primarily by directly inhibiting bioconversion, and by reducing efflux. Individual extract ingredients could only partly explain this effect. Extensive bioconversion, hence, limited absorption of nobilin in the Caco-2 model and the interplay between conjugation and efflux was shown to provide a possible mechanism for absorption increase. Plant extract increased absorption by this mechanism in addition to metabolic enzyme inhibition.
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112 HPLC assay Nobilin and its conjugation products were analysed by HPLC-UV-MS of Agilent series 1200 equipped with a degasser G1379B, a binary pump G1312A, an autosampler G1367B, a thermostat G1330B, a column oven G1316A, a variable wavelength detector G1314B, and a single quadrupole MS detector G6130A.
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ABCC3 p.Gly1316Ala 25477003:112:212
status: NEW