Researchers at the University of California San Francisco have discovered a receptor protein in rodents and humans tuned to respond to temperatures of 120 degrees Fahrenheit and higher - by far the hottest temperatures for which a nerve receptor has been identified.

The protein may be part of a network of mammalian nerve receptors coordinated to detect a wide range of temperatures, but it almost certainly has other as-yet-unknown functions, the researchers report in the current issue of the journal Nature.

The discovery was made as a result of searching the bank of known human gene sequences for a close match to the protein that responds to capsaicin, the molecule that gives hot peppers their bite. Two years ago, the same research team identified the capsaicin receptor, which enables us to detect the heat of chili peppers, as well as temperatures of around 100 degrees.

"While the capsaicin receptor is a very exclusive protein, restricted to sensory nerves, this new protein is more of a generalist," said David Julius, Ph.D., senior author on the Nature paper and associate professor of cellular and molecular pharmacology at UCSF. "It is found on sensory nerves as the capsaicin receptor is, but we also found evidence of it in the brain and spinal cord, in the spleen and intestines. Clearly, in these sites it must be responding to something other than temperature."

Whatever the full function of VRL-1, its discovery holds promise for better understanding pain and developing drugs to block pain, Julius said. "The number of targets to relieve pain is limited. Any discovery of a receptor for extreme temperatures or other noxious stimuli broadens the range of targets for which you can develop candidate drugs."

With the knowledge they have gained of the receptor's gene sequence, the scientists can start to study its function, a major boost to the effort to develop new drugs against pain.

The receptor, known as VRL-1, may respond to some stimulus o
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
31-Mar-1999