This K05 Senior Scientist Award is to support Dr. Jean M. Bidlack's research activities.
The specific aim of this award is to provide Dr. Bidlack with some release time from grant writing, teaching and administrative responsibilities to cover her salary. This award will allow her to devote the majority of her time to research and the training of graduate students and postdoctoral fellows. Dr. Bidlack will expand her research in studying the expression and regulation of opioid receptors on immune cells. Also, she will continue her studies on medications development for the treatment of heroin and cocaine abuse. These goals will be accomplished within the framework of two RO1 grants and three subcontracts from NIDA. Training activities will be supported by a NIDA Training Grant (T32DA07232). The first project (DA04355 and DA09676) is focused on determining which cells from the immune system express mu, delta and kappa opioid receptors. Studies over the past two years have demonstrated the ability to localize the kappa opioid receptor on mixed immune cell populations by the use of an indirect immunofluorescent amplification procedure combined with flow cytometry and the use of cell surface markers. New fluorescent probes will be evaluated to determine if they can be used to localize mu and delta receptors on lymphocytes. A new area of research involves determining if a protein expressed by the human herpes virus 6 and a homolog of the opioid receptor, based on amino acid sequence, is in fact a functional opioid receptor. This protein will be expressed in COS-7 cells; binding and second messenger studies will determine if the protein is a new functional opioid receptor. The second project (DA03742, DA01674 and U19DA11007) involves evaluating new compounds for their potential as candidates for the treatment of drug abuse. The working hypothesis for which we have produced experimental support is that compounds which release dopamine from the nucleus accumbens promote drug-seeking behavior and those which prevent release of this transmitter prevent drug-seeking behavior. It is known that kappa agonists and mu antagonists inhibit dopamine release in the nucleus accumbens. In collaboration with chemists and behaviorists, we will continue our biochemical and behavioral characterization of new compounds, particularly kappa agonists and mu antagonists. Collectively, these projects will provide new information on the localization and function of the multiple opioid receptors on immune cells and on HHV-6. Also, they will advance efforts in developing drugs to treat cocaine and heroin abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
1K05DA000360-01
Application #
2544645
Study Section
Special Emphasis Panel (ZDA1-KXA-N (25))
Program Officer
Sharp, Charles
Project Start
1998-02-01
Project End
2003-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Rochester
Department
Pharmacology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Sromek, Anna W; Provencher, Brian A; Russell, Shayla et al. (2014) Preliminary pharmacological evaluation of enantiomeric morphinans. ACS Chem Neurosci 5:93-9
VanAlstine, Melissa A; Wentland, Mark P; Alvarez, Juan et al. (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 23:2128-33
Provencher, Brian A; Sromek, Anna W; Li, Wei et al. (2013) Synthesis and pharmacological evaluation of aminothiazolomorphinans at the mu and kappa opioid receptors. J Med Chem 56:8872-8
Hoot, Michelle R; Sypek, Elizabeth I; Reilley, Kate J et al. (2013) Inhibition of G??-subunit signaling potentiates morphine-induced antinociception but not respiratory depression, constipation, locomotion, and reward. Behav Pharmacol 24:144-52
Neumeyer, John L; Zhang, Bin; Zhang, Tangzhi et al. (2012) Synthesis, binding affinity, and functional in vitro activity of 3-benzylaminomorphinan and 3-benzylaminomorphine ligands at opioid receptors. J Med Chem 55:3878-90
Wentland, Mark P; Jo, Sunjin; Gargano, Joseph M et al. (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 22:7340-4
Zhang, Bin; Zhang, Tangzhi; Sromek, Anna W et al. (2011) Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for ?, ?, and ? opioid receptors. Bioorg Med Chem 19:2808-16
Zhang, Tangzhi; Yan, Zhaohua; Sromek, Anna et al. (2011) Aminothiazolomorphinans with mixed ? and ? opioid activity. J Med Chem 54:1903-13
Hough, Lindsay B; Nalwalk, Julia W; Yang, Jun et al. (2011) Brain P450 epoxygenase activity is required for the antinociceptive effects of improgan, a nonopioid analgesic. Pain 152:878-87
Balboni, Gianfranco; Salvadori, Severo; Marczak, Ewa D et al. (2011) Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic. Eur J Med Chem 46:799-803

Showing the most recent 10 out of 63 publications