Endogenous opioid peptides reduce pain by binding to opioid receptors, G-protein-coupled receptors expressed in the neuronal circuits involved in pain modulation. Consequently, synthetic opioids have been developed for clinical use to reduce painful sensations in patients. Like endogenous opioid peptides, synthetic opioids reduce pain; however, unlike endogenous opioid peptides, synthetic opioids can cause negative side effects such as addiction, constipation, and respiratory suppression.  The exact neuronal mechanisms underlying the differential effects of synthetic opioids and endogenous opioid peptides are unknown. To help uncover these mechanisms and, therefore, aid in the development of more effective, safer opioid therapeutics, we designed a tool to uncover the opioid-dependent neuronal circuitries involved in pain modulation, addiction, and respiratory suppression. This tool, called SPOTIT (short for Single Protein-chain Opioid Transmitter Indicator Tool), can fluorescently label neurons exposed to opioids (and opioid peptides), thereby uncovering the specific neuronal circuits where the synthetic and endogenous opioids exert their effects on at cellular resolution. Here, we describe SPOTIT’s engineering and show how the general tool motif can be used to design other sensors, such as: a general protein-protein interaction detector and a protease activity detector. Finally, we show how SPOTIT can be useful for both determining the localization of opioids at cellular resolution in an animal brain and high throughput drug screening of new opioid therapeutics.

Development of fluorescent sensors to detect synthetic and endogenous opioids at cellular resolution

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.