Scientists studying how a toxin in shellfish causes diarrhea in humans today reported that they have discovered a mechanism that may help treat cystic fibrosis.

A consortium of seven scientists from the National Institute of Environmental Health Sciences and the Universities of Chicago, Cincinnati and Manchester (UK) described their findings in the Aug. 1 issue of the Journal of Physiology (which is available today on-line at http://physiology.cup.cam.ac.uk/abstracts/1998/index.html). The toxin, okadaic acid, is produced by algae upon which shellfish feed. Although not usually life-threatening, it is a recurrent economic plague on the shellfish industry, particularly in Europe and Japan.

The symptoms of cystic fibrosis arise from there being a genetic block of a major pathway of salt and fluid secretion. The patients' bodies do have another pathway of salt and fluid secretion -- and for many years scientists have sought to develop drugs to increase the activity of this alternative secretory pathway.

Unfortunately, the body normally needs to protect itself from excessive loss of salt and fluid. So cells produce a substance that inhibits the very pathway of fluid secretion that the drugs are designed to increase.

But the new shellfish poisoning study shows that the toxin okadaic acid defeats this built-in fluid conservation mechanism through an interaction with a special class of enzymes known as protein phosphatases.

In the shellfish poisoning, okadaic acid leads to a loss of intestinal salt and fluid, watery diarrhea, cramps and discomfort. Stephen Shears, Ph.D., of NIEHS, proposes that a drug be found to use this same mechanism to stimulate fluid to flow from the cells affected by cystic fibrosis, but without the toxic side effects. The fluid could loosen the mucus that accumulates in the lungs and gut and predispos
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Contact: Tom Hawkins
hawkins@niehs.nih.gov
(919) 541-1402
NIH/National Institute of Environmental Health Sciences
21-Jul-1998