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  • intrinsic lymphatic partition rate  (2)
  • Microdissected nephron segment  (1)
  • 1
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 9 (1992), S. 1617-1621 
    ISSN: 1573-904X
    Keywords: mepitiostane ; epitiostanol ; intrinsic lymphatic partition rate ; lipophilicity ; chylomicron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Substitution of the steroid epitiostanol (EP) at position 17 with methoxycyclopentane yields the extremely lipophilic mepitiostane (MP) with preferential partitioning into the lymph. Most of the MP in the lymph was associated with the core lipids of chylomicrons and very low-density lipoproteins (VLDL), as was also the case for EP. However, the dialysis velocity of EP and MP from lymph to plasma differed greatly; EP, but not MP, was transferred from the lymph to the plasma. This difference was attributed to differences in their unbound fraction in the lymph. Lymphatic transfer and the logP value of several tested steroids correlated well. Therefore, the oral EP prodrug, MP, partitioned into the lymph because of its superlipophilicity and resultant retention in the core lipids of chylomicrons and VLDL.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-904X
    Keywords: mepitiostane ; intrinsic lymphatic partition rate ; intestinal lymphatics ; portal absorption ; epitiostanol ; oleic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Mepitiostane (MP), epitiostanol (EP), and oleic acid were administered to the jejunal loop of mesenteric vein- and thoracic duct-cannulated rats, and the intrinsic lymphatic partition rate (ILPR) of the absorbed compounds was directly determined. When 14C-EP was administered to the jejunal loop, recovery of unchanged EP in the mesenteric blood and the lymph was 7.9 and 0.03% of the administered dose, respectively. In contrast, following administration of 14C-MP, recovery of unchanged MP in the mesenteric blood and the lymph was 1.2 and 15.0%, respectively. Thus, following passage through the mucosal cell, 99.6% of the unchanged EP was partitioned into the blood and 0.4% into the lymph, while for unchanged MP, 7.6% was partitioned into the blood and 92.4% into the lymph. When 14C-oleic acid was administered to the jejunal loop, most of the penetrating oleic acid was incorporated into triglycerides in epithelial cells and transferred exclusively into the lymph. However, of the unchanged oleic acid, only 37.6% was partitioned into the lymph and 62.4% into the blood. The ILPR was 92.4% for MP, 0.4% for EP, and 37.6% for oleic acid. We conclude that the ILPR values indicate the true lymphotropic property of the compounds.
    Type of Medium: Electronic Resource
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