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New hormone may lift Montezuma's vendetta.

Travelers jokingly call it Montezuma's revenge. Physicians know it as traveler's diarrhea. Whatever it's called, this infectious disease can be debilitating to healthy adults and deadly to children, especially those living in developing countries.

But pharmacologists Mark G. Currie and Leonard R. Forte have made a discovery that may someday loosen diarrhea's grip on the gut.

Traveler's diarrhea springs from Escherichia coli bacteria. These microbes make proteins called heat-stable enterotoxins, which bind to receptors on the cells lining the intestines, sparking a series of chemical reactions inside them. The reactions cause the cells to leak water and salt into the gut and to lose their ability to sponge up excess fluids. This flooding produces diarrhea.

In the past, scientists have noted with bewilderment that the body doesn't seem to produce any substance that binds to these receptors. Obviously, the receptors didn't evolve so that disease-causing bacteria could ravage the intestines. "There's no real reason for us to have this receptor unless we make a [protein] for it too," says Currie, a researcher at the Monsanto Co. in St. Louis.

That hunch has now proved correct. Last week, at a meeting of the Endocrine Society in San Antonio, Texas, Currie announced the discovery of a hormone that binds to the same receptors as E. coli's heat-stable enterotoxins. He calls the hormone guanylin.

Currie and Forte, who works at the University of Missouri School of Medicine in Columbia, have compared the hormone and the bacterial protein and have found that they look and behave alike. The researchers showed that guanylin, like the heat-stable enterotoxins, causes the intestinal cells to release water and salt into the gut. Although the hormone's exact role in the body remains unknown, curry speculates that it helps prevent intestinal mucus from drying up. Just as too much fluid in the gut can cause problems, so can too little: If the muscus in the intestines were to dry up, constipation could result.

Currie and Forte are trying to develop a dummy protein that looks enough like guanylin to bind to the receptors but that doesn't affect the cells. If physicians could use such a drug to block all the guanylin receptors in the intestines, E. coli's heat-stable enterotoxins would have nowhere to dock. "We could drastically decrease the effects of the diarrhea," says Currie.

In the Third World, that could mean the difference between life and death. According to the World Health Organization, acute diarrhea kills approximately 3.2 million children in developing countries each year. "They're secreting liters of water a day, dehydrating faster than you can imagine," Currie says.

Other researchers echo the importance of halting E. coli's intestinal foul play. Michael Field, a gastroenterologist at Columbia University in New York City, calls infectious diarrhea caused by E. coli "one of the major health hazards in the world."

Studies of guanylin also have broader scientific implications. "What is that hormone doing in the intestinal tract?" Field asks. Answering this question, he says, will provide "a greater understanding of how the intestinal tract is regulated."
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Title Annotation:traveler's diarrhea; guanylin
Author:Stroh, Michael
Publication:Science News
Article Type:Brief Article
Date:Jul 4, 1992
Words:507
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