Previous studies have demonstrated that a human glutathione conjugate transporter, designated as dinitrophenyl-S-glutathione ATPase (DNP-SG ATPase), catalyzed ATP hydrolysis in the presence of several amphiphilic compounds other than glutathione conjugates (Singhal, S. S., R. Sharma, S. Gupta, H. Ahmad, P. Zimniak, A. Radominska, R. Lester, and Y. C. Awasthi. 1991. FEBSIFed. ). We now demonstrate that DNP-SG ATPase purified from human lung and erythrocyte membranes catalyzed the hydrolysis of ATP in the presence of doxorubicin and its metabolites. Doxorubicin-stimulated ATP hydrolysis by DNP-SG ATPase was saturable with respect to doxorubicin (Km 1.2 and 2.8 MM for the lung and erythrocyte enzymes, respectively). Antibodies against DNP-SG ATPase immunoprecipitated the ATP hydrolyzing activity stimulated by doxorubicin, its metabolites, and glutathione conjugates. Inside out vesicles prepared from erythrocyte membranes took up doxorubicin, daunomycin, and vinblastine in an ATP-dependent manner. The uptake was linear with respect to time and vesicle protein, was dependent on ATP and magnesium, was inhibited by heavy metal salts or by heating the vesicles, and was sensitive to both osmolarity and orientation of the vesicles. The transport had an activation energy of 13 kcal/mol, was saturable with respect to both doxorubicin and ATP (K. values of 1.8 ,M and 1.9 mM, respectively), and was competitively inhibited by glutathione conjugates as well as by a number ofamphiphiles such as daunomycin or vinblastine. Transport was diminished upon coating the vesicles with antibodies against DNP-SG ATPase. Incorporation of increasing amounts of purified DNP-SG ATPase into the vesicles resulted in a linear increase in transport of doxorubicin. These studies demonstrated for the first time that a membrane protein that catalyzed the transport of anionic amphiphilic molecules such as glutathione conjugates could also mediate the transport of weakly cationic antitumor antibiotic, doxorubicin. Notably, the Km of transport was in the range of doxorubi-

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The end point in peptic ulcer disease is a crater in the mucosa. The cause of gastric ulcers seems to be the breakdown of defensive factors, which then allows damage from endogenous and/or exogenous aggressive factors. Aggressive factors are more important in duodenal ulcer formation. Treatment options discussed herein have similar clinical effectiveness, and all have better results than placebo. Selection of a specific agent should be individualized. Helicobacter pylori infection has been implicated in both gastric and duodenal ulcer formation, and use of triple-drug therapy to eradicate or suppress the organism has decreased recurrence rates when maintenance therapy is not used. However, first-line treatment in acute peptic ulcer disease remains the use of antacids, sucralfate (Carafate), or histamine2 receptor antagonists. This approach to therapy is inexpensive, safe, and effective.

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