Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the effects of chronic gentamicin treatment on arginine8-vasopressin (AVP)-dependent cyclic AMP (cAMP) metabolism in rat medullary collecting tubules (oMCT) and medullary thick ascending limbs of Henle's loop (mTALH). Gentamicin attenuated AVP-stimulated cAMP accumulation to a greater extent in the mTALH (delta -51%) than in the oMCT (delta -25%). The mechanism of attenuation differed between segments, and could not be attributed to either direct inhibition of adenylate cyclase activity nor direct potentiation of cAMP-phosphodiesterase activity. These data suggest that the gentamicin-induced decrease in renal concentrating ability may be due at least in part to reduced AVP-dependent cAMP accumulation in the oMCT and mTALH.
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PMID:Impaired cyclic AMP generation in outer medullary tubules of gentamicin-treated rats. 170 20

The effect of aminoglycoside antibiotics on the response of the isolated toad urinary bladder to antidiuretic hormone (ADH) was investigated. Gentamicin and neomycin both acidify the serosal bathing solution and cause a dose-dependent inhibition of the hydroosmotic response to ADH, while streptomycin has minimal effect on media pH and causes no inhibition of the response to ADH. Detailed studies employing gentamicin indicate that acidification stimulates production of PGE2, a known inhibitor of the hydroosmotic response of the toad bladder to ADH. When media pH is rigidly controlled or PGE2 production is inhibited by indomethacin, the inhibitory effect of gentamicin on the response to ADH is ameliorated. These studies suggest that the defect in renal concentrating ability seen as part of aminoglycoside nephrotoxicity could be due, in part, to an acidification-induced, prostaglandin-mediated resistance to the action of ADH.
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PMID:Aminoglycoside toxicity: pH dependent inhibition of ADH response. 301 27

The role of prostaglandins in the development of aminoglycoside-induced acute renal failure was studied in CD-COBS rats (200 to 250 g). The animals were treated with gentamicin (80 mg/kg), acetylsalicylic acid (ASA, 100 or 200 mg/kg), or both drugs or saline for 5 or 10 days. Renal function was studied measuring creatinine clearance, blood urea nitrogen (BUN), and serum electrolytes, urine osmolality, and maximal urinary concentrating capacity after water deprivation and vasopressin administration. Gentamicin toxicity on the proximal tubule was evaluated by measuring urinary excretion of the lysosomal enzyme N-acetylglucosaminidase (NAG). Renal prostaglandin (PG) production was evaluated measuring the concentration of PGE2, PGD2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane B2 (TXB2) in whole renal homogenate after a 15-min incubation at 37 degrees C using gas chromatography-mass spectrometry. Gentamicin alone reduced the glomerular filtration rate (GFR) 20 to 30% after 5 and 10 days of treatment. Combination with ASA potentiated the toxic effect of the aminoglycoside after 10 but not after 5 days of treatment. Similarly, gentamicin reduced the urinary concentrating capacity and addition of ASA worsened the effects. Gentamicin markedly increased NAG excretion but this effect was reduced by ASA, probably as a result of lysosomal stabilization. ASA alone inhibited the production of prostaglandins in renal tissue by 70 to 90% after single or multiple doses. The animals treated with gentamicin alone presented a significant, specific increase in PGE2 production after 10 days of treatment but this increase did not occur when the two compounds were given together. Since PGE2 has a vasodilatory effect in the kidney these results suggest that it may play a specific role in maintaining normal renal blood flow and GFR during the development of aminoglycoside nephrotoxicity. The inhibition of prostaglandin production by nonsteroid anti-inflammatory drugs prevents this compensatory mechanism and worsens the renal damage.
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PMID:Prostaglandins and aminoglycoside nephrotoxicity. 404 89

The present studies were carried out to delineate the mechanism of the polyuric state and renal concentration defect seen after gentamicin. Gentamicin was given at a dosage of 100 mg/kg/day subcutaneously for either 4 or 5 days to Sprague-Dawley rats and resulted in a reversible, polyuric form of acute renal failure. This nonoliguric acute renal failure was accompanied by significant polydipsia and a renal concentrating defect 11 days after gentamicin. To assess the role of polydipsia in the polyuria and renal concentrating abnormality, water intake was restricted in gentamicin-treated animals to match intake of control animals. Elimination of the polydipsia failed to eliminate the polyuria and to improve the renal concentrating abnormality. Postdehydration plasma vasopressin levels were higher in gentamicin-treated than control animals, suggesting that the renal concentrating defect was nephrogenic in origin. Daily urinary prostaglandin E2 excretion was comparable in gentamicin-treated and control animals. However, indomethacin failed to improve urinary concentrating ability, suggesting that the renal concentrating defect was prostaglandin E2 independent. Finally, depressed postdehydration inner medullary tonicity was found in gentamicin-treated animals In summary, gentamicin administration in the rat was associated with a reversible polyuric form of acute renal failure and a renal concentrating defect. This concentration defect was nephrogenic in origin, independent of polydipsia and prostaglandin E2, and was associated with a decrease in inner medullary tonicity.
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PMID:The renal concentrating defect after gentamicin administration in the rat. 657 96