[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.