# STRUCTURE AND FUNCTION OF MRG-FAMILY RECEPTORS

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $582,640

## Abstract

ABSTRACT
 Chronic pain impacts a large proportion of the US population with estimates ranging from 10-40% of adults.
Opioids and related medications are among the most frequently prescribed medications for treating chronic pain,
albeit with considerable risks due to overdose, constipation, addiction and other serious side-effects. Over the
past decades our understanding of the neural circuitry responsible for nociception and anti-nociceptive therapies
has revealed several molecular targets that are potential therapeutic targets for non-opioid pain relieving
medication. Among these are the Mas-related G protein coupled receptors (MRGPRs). The first MRGPR was
discovered in 1986 and since then they have been found to encompass an ~40-member family of GPCRs that
are highly localized to primary sensory ganglia. MRGPRs are divided into 9 major families (viz. MRGPRA
through MRGPRH and MRGPRX) and, of these, the MRGPRX-family of receptors has been highlighted as a
‘primate-exclusive’ group enriched in human sensory neurons.
 We have recently shown that MRGPRX2 likely mediates the mast-cell dependent hypersensitivity responses
caused by prescription opioids and related medications. We have also with collaborators reported that a
polymorphism in MRGPRX4 mediates the preference for mentholated cigarettes among individuals with African
ancestry. The mechanism(s) by which opioids and other drugs interact with MRGPR-receptors is unknown and
here we will elucidate their mechanism(s) by structural biological investigation of these enigmatic receptors.
Using these structures we will discover and optimize chemical tools with which to modulate their function. These
studies will lead to an enhanced understanding of MRGPR-receptor structure and function. The findings may
accelerate the search for medications devoid of MRGPR-mediated side effects and which may function as
therapies for diseases linked to MRGPR-receptor dysfunction.

## Key facts

- **NIH application ID:** 10419804
- **Project number:** 1R01DA055656-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Bryan L. Roth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $582,640
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419804

## Citation

> US National Institutes of Health, RePORTER application 10419804, STRUCTURE AND FUNCTION OF MRG-FAMILY RECEPTORS (1R01DA055656-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10419804. Licensed CC0.

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