Scientists have discovered two compounds in the mammalian brain that appear to be members of a long-sought class of natural painkillers. The proteins, described in tomorrow's issue of Nature, could lead to an analgesic that gives more potent pain relief--with fewer side effects--than morphine.
Morphine and similar narcotics dull pain by binding to 
opioid receptors in the brain. For years,
scientists have hunted for endogenous chemicals that bind to this
receptor, but until now, the only known natural painkillers in the
brain were the endorphins, which bind to other receptor types.
Determined to track down the fugitive proteins, neuroscientist
James Zadina and his colleagues at the Veterans Affairs Medical
Center in New Orleans went fishing. They tinkered with the
structure of a peptide known to bind weakly to 
receptors in the test tube until they had created two
that latched on tight. Like endorphins, these compounds are short
peptides, each just four amino acids long.
Zadina's team tested the compounds' ability to dull pain by injecting them into the brains and spinal cords of mice, then placing each mouse's tail under a hot light. Mice injected with the peptides left their tails in the heat longer than those injected with morphine did. To determine whether these compounds exist naturally in the brain, Zadina's group mixed antibodies to them with ground-up cow brains. The antibodies latched onto the right targets, which were then dubbed endomorphin-1 and endomorphin-2.
"This appears to be a very important finding," says Martin
Wessendorf, a neuroanatomist at the University of Minnesota,
Minneapolis. But to confirm that endomorphins are the real
McCoy--the long-sought -receptor proteins--researchers must still pinpoint
their exact location in the brain and how they function. "We know
that it's in the brain," Wessendorf says, "but we don't know if
it's made or released by nerve cells." There's plenty of enthusiasm
to test the peptides. "They should provide new molecular tools for
dissecting the endogenous opiate pathways in the brain and the
spinal cord," says David Julius, a neuropharmacologist at the
University of California, San Francisco. For his part, Zadina is
ready to develop the next generation of painkillers. Versions of
endomorphins, he says, might work without morphine's side effects,
such as nausea and addiction.
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