090-AP-99
EMBARGOED UNTIL 11 A.M. PDT, WEDNESDAY, JULY 14, 1999
UC IRVINE RESEARCHERS IDENTIFY NERVE CELL RECEPTOR THAT HELPS BRAIN CONTROL EATING BEHAVIOR
Discovery Could Open Door to New Treatments for Obesity, Eating Disorders
Irvine, Calif. -- A team of UC Irvine College of Medicine researchers has discovered a key receptor in the brain that helps control eating behavior. The finding eventually could result in new treatments for obesity and eating disorders.
Olivier Civelli, professor of pharmacology, and senior pharmacology researchers Hans-Peter Nothacker and Yumiko Saito found a receptor, located on nerve cells in the brain, that binds to a nervous system chemical called melanin-concentrating hormone. This hormone--so named because it was identified originally as a pigment regulator in salmon--is considered a major regulator of eating behavior. The researchers report their findings in the July 15 edition of Nature.
"This hormone, which has been shown to regulate how much and how often an animal eats, can work only by binding to this receptor," Civelli said. "Knowing how this receptor works will help us understand the complex ways in which the brain directs eating behavior and may result in new pharmaceuticals that can treat obesity and eating disorders such as anorexia nervosa."
Civelli and his colleagues discovered that the receptor, isolated from rat brains, would bind to melanin-concentrating hormone. In addition, the scientists found that the hormone's receptors were located in areas of the brain called the hypothalamus, hippocampal foundation, olfactory region and nucleus accumbens. These areas control functions such as smell, taste, appetite and feeding urges in animals, all of which work together to regulate how animals--and humans--eat.
Previous studies have shown that the hormone appears to coordinate areas of the nervous system that are involved with eating behavior. Removing melanin-concentrating hormone from animals caused them to be lean; animals that were injected with high amounts of the hormone became obese.
The scientists found the melanin-concentrating hormone receptor through a laborious technique known as an "orphan receptor strategy," in which receptors are tested to see if they bind against neurotransmitters, hormones and other chemicals that exist in the brain, much like bait is used to catch a fish. Once they finally identify a chemical that binds to the receptor, researchers then determine what the receptor looks like and how it functions. In this case, the scientists tested all the chemicals that are present in the brain until they came upon the one chemical that bound to the receptor--melanin-concentrating hormone.
Receptors act as the gateway between nerve cells. When bound to a hormone or other transmitter, they stimulate nerves to fire off their own neurotransmitters, which can initiate certain behaviors or inhibit others.
The scientists will next look at how changes in the brain, the environment and in genes can influence the melanin-concentrating hormone's receptor. "We need to see how genes and conditions like starvation or overeating affect how the receptor reacts to the hormone," Civelli said.
The researchers hope that understanding how the receptor works will help in the development of new drugs that can combat obesity and eating disorders. So far, studies on other proteins that play a role in appetite and eating have not been successful in developing effective drugs against obesity or anorexia. But Civelli hopes that drugs that act on the melanin-concentrating hormone receptors will prove to be more effective than past efforts.
"While obesity is caused by a complex process involving many proteins, nerve cells and genes, we know that this hormone plays a key role in controlling eating behavior. Finding the receptor is a significant step toward seeing if affecting this hormone can treat, or perhaps even prevent, obesity or anorexia," Civelli said.
Zhiwei Wang, Steven Lin and Frances Leslie of the College of Medicine assisted Civelli, Nothacker and Saito in their research.
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Contact: Andrew Porterfield
(949) 824-3969; [email protected]
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