Effect of auranofin (SK&F 39162) on water and electrolyte flux in canine small bowel: a possible diarrheogenic mechanism.
Auranofin (AF) a new antiarthritic gold compound effective when administered orally, frequently causes diarrhea with abnormal stool electrolyte content. Studies were designed to determine the mechanism of the diarrhea caused by AF. In perfused canine Thiry-Vella loops, AF caused significant elevations in effluent volume, osmolarity, and sodium concentration and a significant decrease in potassium concentration. In mucosal homogenates of rat small bowel, AF inhibited sodium, potassium ATPase in a concentration dependent manner. AF did not alter canine colonic smooth muscle activity in vitro. We suggest that AF induced diarrhea results from interruption of normal water and electrolyte absorption by inhibition of enterocyte sodium, potassium ATPase activity.
D000818:Animals; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000503:physiopathology; D003967:Diarrhea / Q000139:chemically induced* / Q000378:metabolism; D004285:Dogs; D004573:Electrolytes / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006046:Gold / Q000031:analogs & derivatives* / Q000494:pharmacology; D017612:Gold Compounds; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014867:Water / Q000378:metabolism*
D002712:Chlorides; D004573:Electrolytes; D017612:Gold Compounds; D014867:Water; D006052:Gold Sodium Thiomalate; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold; C024568:gold tetrachloride, acid; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase