Alexander E. Kalyuzhny , Ph.D.
Research Assistant Professor, Department of Neuroscience
kalyu001@umn.edu

Localization, trafficking and oligomerization of opioid receptors.

Opioid analgesics are currently the first choice drugs for the treatment of pain. Although opioid analgesics have been found to produce antinociception through interaction with pharmacologically distinct G protein-coupled mu-, delta- and kappa-opioid receptors, the mechanism underlying the function of these receptors is not fully understood. For example, a fundamental question remains regarding the functional relevance of heteromeric mu/delta and mu/kappa-opioid receptors.   

My research interests are focused on investigating the mechanisms underlying constitutive and induced heteromerization of opioid receptors using double-transfected HEK-293 cells as a model, as well as primary sensory neurons isolated from the dorsal root ganglia and cultured in vitro.  The study is aimed at determining how opioid receptors form mu/delta- and mu/kappa heteromers as well as at investigating heteromerization of opioid receptors with non-opioid ones, including chemokine CCR5 and CXCR4, and glutamate mGluR5 receptors. In addition, studies are done to reveal the effects of ligands with dual agonist/antagonist activity on receptor trafficking and heteromerization using advanced multi-color fluorescence immunocytochemistry, confocal microscopy, and image analysis techniques. These studies will shed light on the function of opioid receptors and will also help to clarify the role of chemokine and glutamate receptors in modulating the antinociceptive activity of opioid analgesics. 

Selected Publications

Yekkirala AS, Lunzer MM, McCurdy CR, Powers MD, Kalyuzhny AE, Roerig SC, Portoghese PS.  N-naphthoyl-beta-naltrexamine (NNTA), a highly selective and potent activator of μ/kappa-opioid heteromers.  
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5098-103.

Ma J, Zhang Y, Kalyuzhny AE, Pan ZZ.

Emergence of functional delta-opioid receptors induced by long-term treatment with morphine.
Mol Pharmacol. 2006 Apr;69(4):1137-45.

Browning KN, Kalyuzhny AE, Travagli RA.

Mu-opioid receptor trafficking on inhibitory synapses in the rat brainstem.

J Neurosci. 2004 Aug 18;24(33):7344-52.

Kalyuzhny AE.

Immunohistochemical localization of mu-, delta- and kappa-opioid receptors within the antinociceptive brainstem circuits.

Methods Mol Med. 2003;84:79-93.

Kalyuzhny AE.

Simultaneous in situ detection of DNA fragmentation and RNA/DNA oxidative damage using TUNEL assay and immunohistochemical labeling for 8-hydroxy-2'-deoxyguanosine (8-OHdG).

Methods Mol Biol. 2002;203:219-34.

Browning KN, Kalyuzhny AE, Travagli RA.

Opioid peptides inhibit excitatory but not inhibitory synaptic transmission in the rat dorsal motor nucleus of the vagus.

J Neurosci. 2002 Apr 15;22(8):2998-3004.