Sigma receptors are high affinity binding sites for haloperidol and other antipsychotic drugs. Because a number of atypical antipsychotic agents have been found to have a high affinity for sigma receptors, it has been proposed that sigma receptors may represent a common site of action for novel antipsychotic drugs which do not produce extrapyramidal side-effects. Other investigators, however, have proposed that sigma receptors mediate the motor side-effects of dopaminergic antipsychotic agents. Because sigma receptors are the major binding sites for many clinically useful psychopharmacological agents, it may be essential to elucidate their structure and function. A 29kD polypeptide, that has been identified as the binding subunit of the sigma receptor with the photoaffinity label H|-azido-DTG, has now been isolated by SDS-electrophoresis and reversed phase HPLC. This polypeptide has been isolated from the solubilized guinea pig liver membrane, which contains a very high concentration of sigma receptors. This proposal will attempt to perform extensive amino acid sequence analysis on the isolated protein. Furthermore, additional protein(s) that may be part of the sigma receptor complex will be isolated by affinity chromatography using several newly developed affinity chromatography matrices. This work will provide a means to structurally characterize the sigma receptor binding subunit and/or additional proteins of the sigma receptor complex. Structural characterization of the sigma receptor should result in an elucidation of the function of this protein, and, therefore, may lead to a greater understanding of the functional consequences of the binding of psychopharmacological agents to sigma receptors in the brain and other tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH040303-09
Application #
3378352
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1991-04-01
Project End
1994-06-30
Budget Start
1993-04-01
Budget End
1994-06-30
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
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