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Receptor gene found for brain protein.

Receptor gene found for brain protein

Scientists have isolated and cloned a rat gene that codes for a brain protein implicated in human cases of schizophrenia, cocaine addiction and Parkinson's disease. Biologist Olivier Civelli of the Oregon Health Sciences University in Portland and his colleagues say the finding may lead to more effective medications for psychotic and movement disorders. The discovery may also aid in the search for inherited influences in mental disorders, the investigators report in the Dec. 22/29 NATURE.

The brain protein, called the D2 dopamine receptor, can now be reproduced through genetic engineering techniques. Dopamine is a key neurotransmitter, or chemical messenger, in the brain. Dopamine and its two known receptors on the surface of brain cells--the D1 and D2 receptors -- are involved in controlling movement, motivation and emotions.

Work is now underway to unravel the chemical makeup of the rat receptor gene, Civelli says, as well as that of its human counterpart, which the same scientists recently isolated. "The receptor gene provides a direct means for studying the blockage of D2 dopamine-receptors, the presumed mechanism of action for antipsychotic drugs," he notes.

Overactivity of the dopamine system has been linked to schizophrenia for several decades, but the extent of its role in the disorder remains unclear. Drugs that block the D2 dopamine receptor relieve some schizophrenic symptoms but can also produ ce a severe movement disorder known as tardive dyskinesia (SN: 7/20/85, p.45).

Chemically defining the D2 receptor may enable scientists to locate other dopamine receptors, Civelli says. Then drugs might be designed to affect only specific receptors that relieve schizophrenic symptoms without serious side effects.

The Oregon scientists hope to investigate whether there is a surplus of messenger RNA -- a molecule involved in producing proteins -- from the D2 receptor gene in schizophrenics' brains. In addition, they plan to compare the chemical arrangement of the gene in schizophrenics to that observed in healthy individuals.

Reduced dopamine activity is also associated with neurological conditions such as Parkinson's disease. Moreover, cocaine and amphetamines appear to increase dopamine activity by prolonging dopamine's effects on brain cells.

Further study of the D2 receptor gene in these disorders depends on obtaining human brain tissue for laboratory experiments, Civelli says.
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Author:Bower, Bruce
Publication:Science News
Date:Jan 7, 1989
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