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Opioid Receptors: Overview

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...

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Designing a Single Protein-Chain Reporter for Opioid Detection at Cellular Resolution.

Kayla E Kroning^1,2, Wenjing Wang^1,2

¹Life Sciences Institute, University of Michigan, 210 Washtenaw Ave, Ann Arbor, MI, 48109, USA.

Angewandte Chemie (International Ed. in English)

|March 4, 2021

Summary

Researchers developed M-SPOTIT, a novel fluorescent reporter for mu-opioid receptor (MOR) activation. This tool enables rapid, high-resolution detection of opioids in cell cultures and potentially in vivo, advancing pain modulation research.

Keywords:

GPCR cpGFP drug screening fluorescent sensor opioid

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Area of Science:

Neuroscience
Molecular Biology
Pharmacology

Background:

Mu-opioid receptor (MOR) signaling is crucial for pain, reward, and respiration pathways.
Understanding MOR's role in pain modulation requires advanced in vitro screening and in vivo mapping methods for opioids.

Purpose of the Study:

To design and characterize a novel genetically encoded fluorescent reporter for detecting MOR activation.
To develop a tool for high-throughput and high-resolution opioid detection.

Main Methods:

Genetically encoded fluorescent reporter (M-SPOTIT) designed and characterized.
Assessed M-SPOTIT's performance in HEK293T cells and neuronal cultures.
Measured opioid-dependent signal-to-noise ratio (S/N) and EC50 for fentanyl.

Main Results:

M-SPOTIT demonstrated opioid-dependent S/N up to 12.5 in cell culture and 4.6 in neuronal culture.
Detected opioid exposure as rapidly as 30 seconds.
Detected fentanyl with an EC50 of 15 nM.

Conclusions:

M-SPOTIT is a novel tool for detecting MOR activation with persistent fluorescence.
M-SPOTIT enables high-throughput opioid screening in cell cultures and cellular-resolution detection in vivo.
The M-SPOTIT platform can be adapted for other G-protein-coupled receptor sensors.