[Experimental study of the mechanism of auranofin-induced diarrhea].
To clarify the kinetics of cell membrane and intracellular mediators in the process of auranofin (AF)-induced diarrhea, we perfused electrolyte solution containing the oral gold preparation AF, which is a treatment for rheumatoid arthritis, through the rat jejunum, and studied net water and electrolyte transport, Na+, K(+)-ATPase activity, and c-AMP and c-GMP concentrations in the jejunal mucosa. In addition, change in Ca+ concentration in isolated intestinal cells was evaluated using fura-2-acetoxyl-methyl ester. AF significantly suppressed water and electrolyte transport. Mucosal secretion was increased due to elevation of the intracellular Ca+ concentration early in the perfusion period, then due to reduction in the Na+, K(+)-ATPase activity, and increase in the c-AMP concentration late in the perfusion period. Therefore, these cell membranes and intracellular mediators are considered to be involved in the mechanism of AF-induced diarrhea.
Minemori
K
K
Second Department of Internal Medicine, Shiga University of Medical Science.
Nakajo
S
S
Bamba
T
T
Hosoda
S
S
D000818:Animals; D001310:Auranofin / Q000009:adverse effects*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced* / Q000503:physiopathology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D001310:Auranofin; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D002118:Calcium