Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gentamicin is a nephrotoxic antibiotic of the aminoglycoside group, which accumulates within the renal cortex. The present study is an attempt to localize precisely the sites of gentamicin accumulation along isolated tubular segments. We performed autoradiography of 3 H-gentamicin (3H-G) uptake on isolated tubules from kidneys of 6 rabbits previously treated by a single dose of this drug (125 muCi/kg of body wt; 140 microgram/kg of body wt). Isolated tubules were obtained by microdissection following collagenase incubation, 4 hours after 3H-G administration. Autoradiography of single isolated tubular segments was performed according to a dry-film technique. Results were as follows. Almost no gentamicin incorporation (less than 2 silver grains per 150 micrometer2) takes place along the distal parts of the nephron, from the beginning of the loop of Henle to the end of the medullary collecting duct. No differences were visible along these parts of the nephron, whatever their localization, cortical or medullary, In the proximal tubule (PT), we observed a gradual regular increase in 3H-G accumulation, from the glomerulus to the end of the pars recta. The silver grain density progressively increased along this structure from the very early PT (5 per 150 micrometer2) to the last millimeter of the pars recta (40 per 150 micrometers). No clear difference between superficial and juxtamedullary nephrons was detected. The possible mechanisms that could account for this observed variation in 3H-G cellular uptake along the PT are discussed.
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PMID:Gentamicin incorporation along the nephron: autoradiographic study on isolated tubules. 724 87

We established six renal tubular cell lines from definite tubular areas of the kidney of transgenic mice harboring tsSV40 large T-antigen gene. Three are proximal tubular cell lines prepared from the S(1), S(2) and S(3) segments of the proximal tubule and the others are collecting duct cell lines obtained from cortical, outer medullary and inner medullary collecting ducts (CCD, OMCD and IMCD, respectively). To verify the growth properties of these cell lines under different temperature conditions (33 and 39 degrees C), two representative cells were chosen from the proximal tubule (S(1) cells) and from the collecting duct (IMCD cells). From these cells, a daily change in cell number was evaluated as a parameter of cell growth. As might be expected, cell numbers of these cells increased only at 33 degrees C. Similar patterns were also observed with the other cell lines. To observe the different sensitivity to nephrotoxic agents in proximal tubular cell lines, the cells were exposed to nephrotoxic agent, gentamicin, ochratoxin A or cisplatin. Gentamicin (1 mg/ml) dose-dependently decreased cellular ATP levels of the S(1) cells only. In contrast, the effect of ochratoxin A (10(-6) M) was most pronounced in the S(2) cells, and that of cisplatin (10 microg/ml) in the S(3) cells. To characterize collecting duct cell lines, a hyperosmotic challenge of 700 or 1100 mOsm/l was applied to the cells. At an isoosmotic condition of 300 mOsm/l, the number of cells from the collecting ducts, regardless of their origin, increased continuously during the culture period of 4 days. At an osmotic concentration of 700 mOsm/l, the number of CCD cells decreased, while OMCD cells showed a gradual but a significant increase in cell numbers throughout the culture period. IMCD cells, however, proliferated even at a concentration as high as 1100 mOsm/l, although an initial decrease in cell number was noted on the first day of culture. For confirmation of intracellular free calcium ([Ca(2+)](i)) mobilization, cells were treated with ATP and bradykinin. The [Ca(2+)](i) was increased significantly and immediately by ATP (10(-4) M) in S(1) cells and bradykinin (10(-7) M) in IMCD cells. From the results obtained, it is indicated that renal tubular cell lines from transgenic mice have different sensitivities to nephrotoxic or osmotic stress showing the conservation of the functional characters of the definite part it originated from.
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PMID:Different sensitivity to nephrotoxic agents and osmotic stress in proximal tubular and collecting duct cell lines derived from transgenic mice. 1181 40

Urinary exosomes are nano-sized vesicles secreted into urine from all types of renal epithelial cells and are known to contain possible biomarker proteins for renal diseases. Gentamicin has been reported to decrease the level of renal aquaporin (AQP)2, which is known to be mainly expressed in renal collecting ducts and excreted into the urine via exosomes. In the present study, we investigated whether urinary exosomal AQP2 could serve as a potential biomarker for gentamicin-induced nephrotoxicity, especially collecting duct cell dysfunction. Gentamicin was given to rats intraperitoneally once every day starting on day 0. Gentamicin significantly increased the plasma creatinine concentration from day 5 and beyond. Also, gentamicin induced polyuria and a defective urine concentration mechanism on day 7, suggesting gentamicin-induced collecting duct cell dysfunction. Immunoblot analysis showed that gentamicin significantly increased urinary exosomal AQP2 excretion on day 1 but decreased it on day 7 compared with the control group. Similarly, increased excretion of exosomal tumor susceptibility gene 101 protein, frequently used as an exosome marker protein, was observed on day 1. However, gentamicin did not significantly affect the urinary excretion of exosomal tumor susceptibility gene 101 on day 7. Gentamicin slightly decreased renal AQP2 expression on day 2 and markedly decreased it on day 8. These data strongly suggest that the use of urinary exosomal AQP2 as a biomarker may allow detection of gentamicin-induced collecting duct cell dysfunction. Furthermore, urinary exosomal AQP2 might also be useful for the early detection of gentamicin-induced renal injury in addition to collecting duct injury.
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PMID:Urinary excretion pattern of exosomal aquaporin-2 in rats that received gentamicin. 2533 97