Jean M. Bidlack, Ph.D.
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- Cellular and Molecular Pharmacology and Physiology
- Interdepartmental Graduate Program in Neuroscience
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.
Vanalstine MA, Wentland MP, Alvarez J, Cao Q, Cohen DJ, Knapp BI, and Bidlack JM. (2013) Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. Part 9: Synthesis, characterization and molecular modeling of pyridinyl isosteres of N-BPE-8-CAC (1), a high affinity ligand for opioid receptors. Bioorg Med Chem Lett. [Epub ahead of print]
Hoot MR, Sypek EI, Reilley KJ, Carey AN, and Bidlack JM, McLaughlin JP. (2013) Inhibition of Gβγ-subunit signaling potentiates morphine-induced antinociception but not respiratory depression, constipation, locomotion, and reward. Behav Pharmacol. [Epub ahead of print]
Wentland MP, Jo S, Gargano JM, VanAlstine MA, Cohen DJ, and Bidlack JM. (2012) Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. Part 8. High affinity ligands for opioid receptors in the picomolar Ki range: oxygenated N-(2-[1,1'-biphenyl]-4-ylethyl) analogues of 8-CAC. Bioorg Med Chem Lett. 22:7340-7344.
Neumeyer JL, Zhang B, Zhang T, Sromek AW, Knapp BI, Cohen DJ, Bidlack JM. (2012) Synthesis, binding affinity, and functional in vitro activity of 3-benzylaminomorphinan and 3-benzylaminomorphine ligands at opioid receptors. J Med Chem. 55:3878-3890.
Li Y, Lefever MR, Muthu D, Bidlack JM, Bilsky EJ, Polt R. (2012) Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins. Future Med Chem. 4:205-226.
Dean RL, Eyerman D, Todtenkopf MS, Turncliff RZ, Bidlack JM, Deaver DR. (2012) Effects of oral loperamide on efficacy of naltrexone, baclofen and AM-251 in blocking ethanol self-administration in rats. Pharmacol Biochem Behav. 100:530-537.
Jean M. Bidlack, Ph.D.
University of Rochester
School of Medicine and Dentistry
601 Elmwood Avenue
Rochester, NY 14642