Kelley M. Standifer


Professor of Pharmacology

Department of Pharmaceutical Sciences


B.S. Zoology, Duke University, Durham, NC
Ph.D. University of Florida, Gainesville, FL 


Society on NeuroImmune Pharmacology
Rho Chi
Sigma Xi
American Society for Pharmacology and Experimental Therapeutics
American Association of Colleges of Pharmacy
International Narcotics Research Conference
Society for Neuroscience


My research interests, ultimately, is to develop alternative therapeutic options (to morphine) for the treatment of severe pain. The newest member of the opioid receptor family, opioid receptor like-1 receptor (ORL1), and its endogenous agonist, orphanin FQ/nociceptin (OFQ/N), have been strongly implicated in the development of morphine tolerance. Chronic morphine treatment increases levels of OFQ/N; blocking the actions of OFQ/N significantly reduce the extent to which the analgesic actions of morphine are reduced. Using human neuronal cell lines that natively express mu and ORL1 receptors, we study the cellular mechanisms of ORL1 and mu opioid receptor activation (by the endogenous peptides OFQ/N and Dynorphin, and the synthetic agonists, DAMGO and morphine), and the cellular mechanisms of ORL1- and mu opioid receptor-mediated mu and ORL1 tolerance and cross-tolerance. Acutely, OFQ/N activates protein kinase C (PKC), which activates and translocates G protein-coupled receptor kinase 2 (GRK2) and GRK3 to the cell membrane where GRK2 can quickly desensitize the mu opioid receptor in the presence of a mu opioid agonist such as morphine. Our next step is to determine where these changes occur in vivo, and how they might be manipulated to reduce the extent of morphine tolerance development.  

ORL1 desensitization is produced by GRK3. Tolerance induced by prolonged exposure to OFQ/N and/or morphine treatment also involves GRK. Similar to morphine, prolonged OFQ/N treatment (24 h or more) upregulates GRK levels. Ultimately, though, it is the increased availability of GRK that produces the rapid tolerance and/or cross-tolerance upon challenge with an agonist. We are in the process of studying ORL1 phosphorylation sites, and how mutation of these sites affects receptor



1. Sherry DM, Mitchell R, Standifer KM, du Plessis B (2006) Distribution of Plasma Membrane-Associated Syntaxins 1 through 4 Indicates Distinct Trafficking Functions in the Synaptic Layers of the Mouse Retina. BMC Neuroscience 7:54.

2. Desai AN, Salim S, Standifer KM, Eikenburg DC (2006) Involvement of G protein-coupled kinase (GRK)3 and GRK2 in down-regulation of the a2b-adrenoceptor. J Pharmacol Exp Ther 317, 1027-35.

3. Ramirez VI and Standifer KM (2006) Morphine induces Mu opioid receptor internalization in BE(2)-C human neuroblastoma cells. Soc. Neurosci Abstr

4. Thakker DR, Altememi GF, Mandyam CD and Standifer KM (2006) Naloxone Benzoylhydrazone activates extracellular signal-regulated kinase and regulates nociceptin peptide receptor activity. International Narcotics Research Conference, St. Paul, MN.

5. Gee JS and Standifer KM (2005) Mu Opioid Receptor Internalization Induced by Dynorphin A(2-17) through Activation of the Opioid Receptor Like-1 Receptor (ORL-1), Sigma Xi, University of Houston. Received outstanding poster award for undergraduate student*


University of Oklahoma Health Sciences Center

College of Pharmacy, Department of Pharmaceutical Sciences

P.O. Box 26901

Oklahoma City, OK 73126-0901

Phone: (405) 271-6593, ext. 47333

Fax: (405) 271-7505