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John Streicher, Ph.D., assistant professor of biomedical sciences, authored an article titled “Functional Selectivity of 6’-Guanidinonaltrindole (6’-GNTI) at _-Opioid Receptors in Striatal Neurons” that was published in the Journal of Biological Chemistry on August 2nd, 2013.  (J Biol Chem. 2013 Aug 2;288(31):22387-98)

The article explores a property of the _-Opioid Receptor (KOR) known as “functional selectivity” or “signaling bias” in which a molecule binding to the receptor can specifically activate one downstream signaling pathway over another.   The KOR is a G protein-coupled receptor (GPCR), and while it has the potential to induce analgesia and helps decrease drug-taking behaviors, KOR activation also has unpleasant side effects.  KOR signaling is mediated via G protein pathways and _arrestin pathways, and previous work in the field has suggested that _arrestin2 signaling is responsible for the negative side effects of KOR activation.

In this article, Streicher and colleagues demonstrate that the drug 6’-GNTI specifically induces G protein pathways over _arrestin pathways and that this specificity persists in striatal neurons.  This demonstration of functional selectivity at the KOR, especially the revelation that it exists in the endogenous, neuronal setting, has major significance for drug discovery and could pave the way toward designing improved pain therapies for the KOR that specifically target pain without producing unwanted side effects.