The researchers, who discovered the hormones, said in today's issue of Cell that further research into these neuropeptides -- proteins found in nerve cells -- and receptors may reveal ways to inhibit eating. The hormones were found to stimulate the appetite of laboratory rats. The neuropeptides, or ligands, which are called orexin-A and orexin-B, and the receptors, OX1R and OX2R, allude to the Greek word orexis, for appetite.

"These receptors and ligands regulate feeding behavior, which is a very important area of medical research," said Dr. Masashi Yanagisawa, professor of molecular genetics and Howard Hughes Medical Institute (HHMI) investigator. "This is an excellent area for further drug research to determine whether orexins and their G protein-coupled cell-surface receptors can be targeted to suppress eating habits."

In the first part of their investigation, the scientists found the receptors, which are closely related proteins. When bound to ligands, the receptors trigger a G protein, which in turn sets off a series of messages to turn on or turn off genes. Next, they found the two ligands, members of a previously unidentified family of neuropeptides, which bind with OX1R and OX2R to begin the signaling cascade. These proteins are located in a portion of the brain called the lateral hypothalamus, the region that controls appetite.

After determining that they had the locks (receptors) and keys (ligands) that fit together to begin the intercellular communication process, the investigators tested it on rats. They used catheters to administer some of the neuropeptides to the animals' brains and found that the proteins stimulated food consumption.

"When we limited the
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Contact: Susan A. Steeves
ssteev@mednet.swmed.edu
(214) 648-3404
UT Southwestern Medical Center
20-Feb-1998