Scientists Identify Receptor That Can Regulate Appetite


Scientists at UC Irvine and in Britain have isolated a long-sought receptor in the brain that is crucial in controlling appetite, a finding that could make possible the development of powerful new drugs to wage war on obesity and anorexia.

The finding, reported in separate studies published in the journal Nature today, holds out the possibility that researchers could develop drugs to block nerve cells activated by the receptor, thus inhibiting the impulse to eat, said scientists.

The discovery was made simultaneously by Olivier Civelli, a professor in neuropharmacology at UC Irvine's College of Medicine, and researchers for SmithKline Beecham Pharmaceuticals in Britain, led by Jon Chambers.

"It opens the door to doing pharmacological research of this system," Civelli said. "It has much potential in the field of food consumption and energy metabolism."

Although Civelli and his team, which included senior pharmacology researchers Hans-Peter Nothacker and Yumiko Saito, did their work in rats, the hormone that targets the receptor plays the same role in humans. Many human neurotransmitters and receptors were first discovered in rodents.

"This is very interesting that they identified a receptor and it is known to regulate feeding behavior," said Jean Shih, a molecular biologist at the USC School of Medicine.

Drugs that could bind with this receptor and block it--so-called antagonists--are at least five years away from the market, said scientists. Similar blocker drugs have been developed for treatment of schizophrenia, asthma, depression, heart disease and other illnesses.

"Every single pharmaceutical company will be trying to identify the antagonist of this molecule in animals and humans," said Dr. Jeffrey Flier of the Harvard Medical School.

About 55% of Americans are overweight and 22% are classified as obese, meaning they are at least 30% overweight, so the market for any drug would be large. In addition to providing a new approach to overeating, the research could lead to treatments for diseases such as anorexia that would work by stimulating--rather than blocking--the receptor, scientists said.

The chemistry of eating behavior is very complex, though, involving various hormones and receptors in the brain, so isolating this receptor and its function may be only one piece in solving the appetite puzzle.

Civelli suggested, however, that the receptor identified in the new research is especially critical because it is heavily concentrated in areas of the brain commonly associated with sensory perception, taste, smell and motivation.

The average human brain has millions of the newly identified receptors, named MCH receptors after melanin-concentrating hormone, the hormone that binds with them. Receptors act as a gatekeeper for neurons, triggering them--and thereby sensations such as hunger--when they come in contact with the correct hormone.

The melanin-concentrating hormone was labeled as a major regulator of appetite three years ago by a team of Harvard researchers, including Flier and his wife, Eleftheria Maratos-Flier, triggering a fevered search for the receptor it binds to. The group first stimulated eating in rats by injecting their brains with the hormone and last year developed lean mice by genetically altering them so that they produced no MCH.

But the receptor had remained a mystery.


Times Medical Writer Thomas H. Maugh II contributed to this story.


Blocking the Urge to Eat

Researchers at UC Irvine and in Britain have isolated a nerve cell receptor in the brain that helps regulate appetite. With the discovery, pharmaceutical companies are expected to work on new drugs that would prevent the appetite-controlling hormone from binding with the recently isolated receptor.

Graphics reporting by BRADY MacDONALD / Los Angeles Times

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