Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Labeled estrogen was injected into one of the renal arteries of baboons and urine was collected separately from each ureter via ureterostomy at various time intervals over a period of 7 h; the urinary metabolites were analyzed by DEAE-Sephadex chromatography and enzyme hydrolyses. Identification of the aglycones was made by TLC and co-crystallization upon admixture with authentic compounds. When [3H]estradiol-17beta (E2) was injected into one of the renal arteries, the major metabolites were [3H]E2-3-glucosiduronate (E2-3G) and [3H]estrone-3-glucosiduronate (E1-3G); [3H]E2-3G was excreted predominantly into the urine from the injected side during the initial 30 min after injection. Formation of [3H]E1-3G was not detectable for the first 5 min in the urine from either side. However, its excretion gradually increased and the amount was almost equal from both sides in the later hours of collection. Injection of [3H]E1 revealed ready conjugation (as E1-3G) by the kidney without significant reduction at position-17. When E2-3G, labeled with 3H at positions 6,7 and with 14C in the glucuronic moiety, was injected, it was quickly excreted in the urine of the injected side. The ratio of 3H/14C of E2-3G excreted in the urine was the same as that of the injected E2-3G. In the later periods, E1-3G, which had a slightly increased 3H/14C ratio, appeared in the urine. These results indicate that E2 and E1 are conjugated directly in the kidney to form the 3G which is excreted into the urine and that effective dehydrogenation or reduction of the steroids in vivo does not take place in the kidney. The results also show that conjugated E2 (E2-3G) is quickly excreted by the kidney of the baboon without any change in its form and that the E2-3G is dehydrogenated to E1-3G during its general circulation without significant prior removal of the glucuronic moiety. When [3H]estriol (E3) was injected, facile glucuronidation to E3-16G by the kidney was shown. Injection of an equimolar mixture of [14C]E3 and [3H]E2 showed rapid excretion of [14C]E3-16G as opposed to the slower excretion of [3H]E2-3G. These results suggested that the active sites of these conjugating enzyme systems in the kidney may be different.
 ...
PMID:In vivo and in vitro conjugation and metabolism of estrogens by the baboon kidney. 82 21

Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of the muscle. At present, five different families of isoenzymes of PDE exist that show a distinct species-specific and organ-specific distribution. The aim of the present study was to analyze the PDE isoenzymes present in the human ureter and to evaluate the functional effects of isoenzyme-specific inhibitors in this tissue. Normal ureteral tissue was obtained during radical nephrectomies, homogenized, centrifuged, and the supernatant fraction was separated using DEAE-Sephacel anion-exchange chromatography. PDE assay was then performed and the isoenzymes characterized on the basis of their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. In vitro, longitudinal ureteral strips as well as ureteral rings were precontracted, and different selective and nonselective PDE inhibitors were added incrementally. Three different PDE isoenzymes were identified: PDE I (Ca/calmodulin-stimulated), PDE II (cyclic guanosine monophosphate-stimulated), and PDE IV (cyclic adenosine monophosphate-specific). All PDE inhibitors relaxed the strips dose-dependently with an EC50 of 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The existence of three different PDE isoenzymes was shown in this study. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low effect on the systemic circulatory parameters, may open a possibility of using selective PDE IV inhibitors in the treatment of ureteral colics or ureteral stones.
 ...
PMID:Phosphodiesterase isoenzymes in human ureteral smooth muscle: identification, characterization, and functional effects of various phosphodiesterase inhibitors in vitro. 858 63