More MS news articles for July 2001

Trace Amines May Directly Influence Neurological Disorders

http://www.medscape.com/reuters/prof/2001/07/07.17/20010716scie005.html

WESTPORT, CT (Reuters Health) Jul 16 - Researchers have identified mammalian receptors for trace amines, thus providing the first evidence that trace amines may act as neurotransmitters or neuromodulators in vertebrates.

"There's a huge literature on trace amines that get up- and downregulated in various neurological and psychological disorders, and which are affected by things like antidepressants," Dr. Beth Borowsky, of Synaptic Pharmaceutical Corporation in Paramus, New Jersey, told Reuters Health.

"We didn't know if they were acting as neurotransmitters themselves or if they were just metabolic products of more common neurotransmitters, like serotonin and dopamine and norepinephrine," she added.

Trace amines, which occur in low concentrations in mammalian tissues, include tyramine, beta-phenylethylamine, tryptamine, and octopamine, Dr. Borowsky and associates note in the Early Edition of the Proceedings of the National Academy of Sciences for July 17.

The investigators identified four 'G' protein-coupled receptors for trace amines in humans. The research group tested one of these, the TA-1 receptor, against several potential targets, Dr. Borowsky told Reuters Health.

"It turns out this is a fairly promiscuous receptor, whereas the serotonin receptor responds only to serotonin. TA-1 responds to a number of trace amines that are similar in sequence," she said. It is activated by tyramine, ß-phenylethylamine, and octopamine, and binds tyramine and ß-phenylethylamine with high affinity.

Using reverse transcriptase polymerase chain reaction analysis, TA-1 mRNA in the human brain was found to be present in highest concentrations in the amygdala, "possibly linking trace amine receptors to affective disorders," the investigators write.

They note that the human trace amine receptor genes map close to a susceptibility locus for schizophrenia, and that ß-phenylethylamine is elevated in the urine of schizophrenic patients.

According to Dr. Borowsky, the group's current efforts are directed toward "coming up with selective antagonists and agonists that target these specific receptors, but not the neurotransmitter transport system." The investigators will then test these compounds to see if they induce depression or psychosis, or if antidepressant or antipsychotic effects are elicited.

Concluded Dr. Borowsky, "If they do block or stimulate the receptors, the next question will be, can we use them to change the course of the disease?"

Proc Natl Acad Sci July 10, 2001. www.pnas.org/cgi/doi/10.1073/pnas.151105198.
 

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