Cellular mechanisms of drug-induced papillary necrosis.
2-Bromoethylamine hydrobromide (BEA) causes complete papillary necrosis within 24-hr of i.v. administration. The mechanism of this effect is unknown. To characterize further the effect of BEA in transporting epithelia, the urinary bladders of toads and turtles were exposed to varying concentrations of BEA in vitro. In the toad bladder, both cyclic AMP- and vasopressin-stimulated water flow were significantly inhibited after 3 hr of exposure to BEA at a concentration as low as 2.5 X 10(-4) g/ml; after 1 and 2 hr no effect on water transport was observed. Serosal administration of BEA to both toad and turtle bladders significantly inhibited sodium transport to 54% of control at the end of 3 hr. The effect on sodium transport was seen as early as 10 min. The threshold for the effect on sodium transport occurred at a concentration less than that observed for water transport. By contrast, BEA had no effect on hydrogen ion secretion in the isolated turtle bladder over a wide range of concentrations. In fact, after 1 hr, BEA significantly stimulated hydrogen ion secretion. In homogenates of stripped turtle bladder mucosa, BEA significantly inhibited total Na-K adenosine triphosphatase and ouabain sensitive Na-K adenosine triphosphatase. Thus, in anuran membranes, BEA inhibits water and sodium transport but has no effect on acidification. These results suggest that its action in vivo may be related to alterations in cell volume regulation resulting from inhibition of sodium transport rather than a nonspecific toxic effect on the inner medullary epithelium.
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D000818:Animals; D001834:Body Water / Q000378:metabolism; D002024:Bufo marinus; D000242:Cyclic AMP / Q000494:pharmacology; D005021:Ethylamines / Q000494:pharmacology*; D006859:Hydrogen / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000473:pathology*; D009336:Necrosis; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology
D005021:Ethylamines; C004504:2-bromoethylamine; D014667:Vasopressins; D006859:Hydrogen; D012964:Sodium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase