The purpose of this project is to characterize at the molecular level the action of Escherichia coli heat-stable (ST) enterotoxin. Using a combination of molecular techniques, emphasis will be placed on identifying the sequence of events in the action of ST enterotoxin. These studies will determine what functional role calcium, guanylate cyclase and metabolites of arachidonic acid play in the action of ST enterotoxin on intact and ruptured membrane preparations of rat basophilic leukemia (RBL) cells and isolated rat intestinal enterocytes. The effect of ST enterotoxin on Ca++ ATPase, phospholipase A2, and ADP-ribosylation is also under consideration. In further studies, pharmacologic and chemical agents that inhibit calcium uptake and prostaglandin synthesis will be tested for ability to alter the ST-mediated response. Before effective therapeutic intervention can be developed, the molecular action of ST enterotoxin must be understood and the role of pharmacologic agents that alter the ST-mediated response must be investigated. Knowledge related to the probable use of pharmacologic agents in diarrheal disease(s) will be advanced.
