BIO-AND IMMUNO-CHEMICAL STUDIES ON OPIATE RECEPTORS

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The purpose of this research is to combine the expertise of two laboratories in fundamental studies on the biochemistry and molecular biology of opiate receptors. Our laboratory has developed an immunochemical approach towards characterizing the receptors. In particular, this has involved the production of anti-idiotypic antibodies which competitively inhibit drug binding to the receptors. The other laboratory has been one of the world leaders in developing solubilization methods which are applicable to these particular membrane bound receptors. Anti-idiotypic antibodies which bind specifically to opiate receptors are to be used as probes in biochemical, molecular biological and immunocytological studies on opiate receptors. In the biochemical work the antibodies will be used in conjunction with reversible protein-protein cross-linking agents in order to solublize the entire receptor complexes. These will then be purified using immunoaffinity techniques in order to obtain receptor complexes which may be studied both in their entirtey as well as broken into their components for detailed characterization. In molecular biological work the anti-idiotypic antibodies will be used as probes for translational products in recombinant DNA experiments. With these techniques opiate receptor proteins will be sequenced indirectly. This information will be further used, in a second stage of the work, to sequence the genomic arrangements which give rise to the receptors. The immunocytological work will be directed towards exploring methods directed towards the end of fractionating opiate receptor-bearing neurons from the general population of central nervous tissue neurons. This latter, combined with the molecular biological information will ultimately lead to studies of; the control of opiate receptor expression in cells, the primary events following ligand recognition by the receptors, and the roles of receptors in pain path-ways and addictive liability of drugs.