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  • 1
    Electronic Resource
    Electronic Resource
    Intra- and inter-nephron heterogeneity of gluconeogenesis in the rat: effects of chronic metabolic acidosis and potassium depletion (1986)
    Springer
    Pflügers Archiv 407 (1986), S. 1-7 
    Details
    ISSN: 1432-2013
    Keywords: Renal gluconeogenesis ; Chronic metabolic acidosis ; Potassium depletion ; Microdissected nephron segment ; Superficial nephron ; Juxtamedullary nephron ; Nephron heterogeneity ; Substrate specificity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The intra- and inter-nephron heterogeneity of renal gluconeogenesis within rat proximal tubules and the effects of chronic metabolic acidosis and chronic potassium(K)-depletion were studied using isolated proximal tubules of rats by directly measuring glucose synthesized. The gluconeogenic activity from pyruvate and glutamine in control rats was almost limited to within the early proximal tubule (S1: 45.4±5.7 pmol/mm/60 min from pyruvate; 58.0±6.0 from glutamine). Very low, but detectable gluconeogenesis was observed in the middle portion of the proximal tubule (S2:9.9±2.2 from pyruvate; 4.8±1.1 from glutamine). The rate of glucose production in the terminal proximal tubule (S3) was negligible. Furthermore, gluconeogenesis from glutamine of superficial (SF) nephrons was significantly higher than that of juxtamedullary (JM) ones, whereas no difference was seen in gluconeogenesis from pyruvate. In acidotic and K-depleted rats, significant increase could be seen in S1 and S2, but the increase in S3 was not significant. By the serial determination in acidosis, the glucose production from both substrates was found to be the highest at the second 1 mm segment from the glomerulus, and it decreased downward along the proximal tubule. In acidosis, glucose production from both substrates in SF nephrons and that from glutamine in JM ones were elevated significantly compared with the control, but that from pyruvate in JM nephrons did not change. These results suggest that S1 of the SF nephron plays the most important role in gluconeogenesis in the control, whereas S1 of the JM nephron and S2 contribute to gluconeogenesis in acidotic and/or possibly K-depleted rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00580712
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Stereoselective pharmacokinetics of ibuprofen in rats: effect of enantiomer-enantiomer interaction in plasma protein binding (1997)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 9 (1997), S. 354-361 
    Details
    ISSN: 0899-0042
    Keywords: ibuprofen ; enantiomers ; stereoselective ; interactions ; plasma protein binding ; rat ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Stereoselective pharmacokinetics of ibuprofen (IB) enantiomers were studied in rats. Unidirectional conversion from R-ibuprofen (R-IB) to S-ibuprofen (S-IB) was observed following intravenous administration. S-IB concentrations in plasma following racemate administration were simulated according to a conventional compartmental model using the parameters obtained after the administration of individual enantiomers, and resulted in overestimation of S-IB concentrations.Binding of IB enantiomers measured in rat plasma was stereoselective, the binding of R-IB being more favorable than that of S-IB. Moreover, there are interactions between IB enantiomers in binding, which may cause the increase of distribution volumes of IB enantiomers in the presence of their antipodes. Hence simulated S-IB concentrations according to a conventional compartment model were significantly greater than those observed. Indeed, when the enantiomer-enantiomer interactions were taken into account, simulation of S-IB concentrations in plasma following racemate administration was in good agreement with observed values. Therefore, interactions between stereoisomers as well as dispositional stereoselectivity have to be considered when pharmacokinetics of stereoisomers after administration of the racemate are compared to those after administration of individual isomers. Chirality 9:354-361, 1997. © 1997 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Stereoselectivity and enantiomer-enantiomer interactions in the binding of ibuprofen to human serum albumin (1997)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 9 (1997), S. 643-649 
    Details
    ISSN: 0899-0042
    Keywords: ibuprofen ; stereoselective ; binding ; HSA ; interaction ; fluorescent ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Binding of ibuprofen (IB) enantiomers to human serum albumin (HSA) was studied using a chiral fluorescent derivatizing reagent, which enabled the measurement of IB enantiomers at a concentration as low as 5 × 10-8 M. Scatchard analyses revealed that there were two classes of binding sites for both enantiomers. For the high affinity site, the number of the binding sites was one for both enantiomers, and the binding constant of R-IB was 2.3-fold greater than that of S-IB. The difference in the affinity at the high affinity site may result in the stereoselective binding of IB enantiomers at therapeutic concentrations. It was confirmed that the high affinity site of IB enantiomers is Site II (diazepam binding site) by using site marker ligands. Also, significant enantiomer-enantiomer interactions were observed in the binding. The binding data were quantitatively analyzed and a binding model with an assumption of competitive interactions only at the high affinity site simulated the binding characteristics of IB enantiomers fairly well. Chirality 9:643-649, 1997. © 1997 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Stereoselective renal secretion of carbenicillin in rabbits: Role of the organic anion transporter at the renal brush border membrane (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 349-357 
    Details
    ISSN: 0899-0042
    Keywords: carbenicillin ; stereoselective ; secretion ; transport ; rabbit ; membrane vesicles ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Stereoselectivity in the renal secretion of carbenicillin (CBPC) was studied in rabbits. Significant renal secretion of CBPC was observed in vivo, with the secretion of the S-epimer being greater than that of the R-epimer. Stereoselective transport of CBPC was further studied in vitro using basolateral and brush border membrane vesicles prepared from rabbit kidneys. The transport of CBPC by the organic anion transporter into the basolateral membrane vesicles (BLMV) was not stereoselective. In contrast, a distinct stereoselectivity was observed in the transport of CBPC by the organic anion transporter into the brush border membrane vesicles (BBMV), with the transport of the S-epimer being more favorable. Significant epimer-epimer interactions were also observed in the transport into BBMV. The stereoselectivity of the transport of CBPC was calculated from the kinetic parameters with consideration of epimer-epimer interactions and was similar to that observed in vivo. It was concluded that the observed stereoselectivity in the renal secretion of CBPC in vivo reflected that of transport via the organic anion transporter located at the brush border membrane. Chirality 10:349-357, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Stereoselective binding of carbenicillin epimers to human serum albumin (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 201-206 
    Details
    ISSN: 0899-0042
    Keywords: carbenicillin ; stereoselective ; binding ; HSA ; interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Binding of carbenicillin (CBPC) epimers to human serum albumin (HSA) was found to be stereoselective. Epimer-epimer interaction was also observed in the binding to HSA. There were at least three binding sites on HSA for CBPC epimers, one of which (stereoselective site) was more in favor of S-CBPC than R-CBPC. At the stereoselective site, the binding constant of S-CBPC was approximately 4-fold greater than that of R-CBPC. The affinities to other binding sites (non-stereoselective sites) were similar between the epimers, and the affinity of S-CBPC of the non-stereoselective sites was much smaller than that for the stereoselective site.R-CBPC and S-CBPC appeared to displace each other at all the binding sites, i.e., the binding of the epimers was competitive at the non-stereoselective sites as well as at the stereoselective site. By using site marker ligands, it was revealed that CBPC epimers may bind to Site I (warfarin binding site), but not to Site II (diazepam binding site). A binding model with an assumption of competitive interactions at all the binding sites simulated the binding characteristics of CBPC epimers fairly well. © 1996 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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