Structure and Function of Opioid Receptors

This laboratory is interested in studying the structure and function of opioid receptors, expressed in the brain and on cells from the immune system. We are characterizing novel opioids that may have the potential for becoming a medication to cocaine and heroin abuse. All drugs of abuse act on the dopamine reward pathway, the same pathway that is activated by any pleasurable experience. The activation of this pathway leads to the reinforcing effects of pleasurable effects, such as eating. Drugs that are addicting increase the release of dopamine in the nucleus accumbens, a discrete brain region. Because these drugs increase dopamine levels to a much greater extent than normal physiological events that produce a pleasurable effect, drugs, such as cocaine and heroin, produce a strong reinforcing effect. In collaboration with chemists and behaviorists at Rensselaer Polytechnic Institute, Harvard Medical School, and Torrey Pines Institute for Biomedical Sciences, we are trying to develop medications that will decrease the dopamine release that is induced by drugs of abuse. By decreasing the dopamine levels, the reinforcing effects of drugs of abuse will be reduced.

Another project in the lab is to characterize the structure and function of the multiple opioid receptors. The opioid receptor family is a member of the G-protein coupled receptor family. Recently, we have shown that the kappa opioid receptor is present as an oligomer in the natural state. Previously, it had been thought that receptors existed as monomers. We have shown that the oligomeric form of the receptor is the active form, which can transduce opioid agonist binding to a physiological effect. We are examining the role of the oligomers, dimers, and monomers in desensitization of the receptor. In addition, we are studying the formation of heterodimers and oligomers between mu and delta opioid receptors.

A third project involves determining which cells from the immune system express the multiple opioid receptors. We have developed a sensitive fluorescent method which when combined with flow cytometry and cell surface markers allow us to determine which types of lymphocytes express the receptor. Knowing which cell types express the receptor allows us to start determining the function of the multiple opioid receptors on lymphocytes.

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