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Updated: Sep 14, 2025

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
Homeostatic scaling of dynorphin signaling by a non-canonical opioid receptor
Xiaona Li1, Nathan D Winters1, Shubhi Pandey1
1Department of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Abstract:
The endogenous opioid system provides powerful control over emotions, nociception, and motivation among many other fundamental nervous system functions. Its major components include a panel of opioid peptides that activate four canonical inhibitory opioid receptors. However, its regulatory principles are not fully understood including the existence of additional receptors and other elements. In this study we report the identification of a receptor for the opioid peptide dynorphin. By conducting a screen of a custom library of neuropeptides, we found that orphan receptor GPR139 binds to and is activated by a series of dynorphin peptides. Unlike other opioid receptors, GPR139 couples to Gq/11 and avoids β-arrestin, providing excitatory signaling that homeostatically scales the inhibitory response of neurons to dynorphin. This introduces a non-canonical dynorphin receptor as an essential component of the opioid system.
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