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MrgprA3 shows sensitization to chloroquine in an acetone-ether-water mice model
1aDepartment of Physiology, School of Medicine and Life Sciences bKey Laboratory of Prevention and Treatment of Chinese Medicine in Neurological Disease, Nanjing University of Chinese Medicine cDepartment of Biochemistry, College of Life Sciences, Nanjing Normal University, Nanjing dDepartment of Physiology, College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, China.
Abstract:
Chronic itch, a distressing symptom of many cutaneous and systemic diseases, significantly impairs quality of life. However, its underlying molecular mechanism is still unclear. Mas-related G protein-coupled receptor A3 (MrgprA3) is considered an itch-specific receptor. MrgprA3 neurons are identified as a class of itch-specific neurons, but the role of MrgprA3 in chronic itch remains elusive. An acetone-ether-water (AEW) model as a histamine-independent itch model is often used in the study of chronic pruritus. In this study, behavioral tests, immunostaining, cell culture, calcium imaging, and other experiments were carried out to examine the expression of MrgprA3. The results showed that the scratching bouts induced by chloroquine increased significantly under the AEW condition; the density of MrgprA3 sensory fibers in the AEW-treated skin area and the number of MrgprA3 neurons in dorsal root ganglia from the AEW model mice also increased significantly. Further analysis showed that the MrgprA3 in mRNA level was also increased after AEW treatment. These results indicated that MrgprA3 played a crucial role in chronic pruritus in the AEW model.
Insights
Chronic itch involves Mas-related G protein-coupled receptor A3 (MrgprA3). Studies show MrgprA3 expression and neuron density increase in a chronic itch model, highlighting its role in pruritus.
Area of Science:
- Neuroscience
- Dermatology
- Molecular Biology
Background:
- Chronic itch significantly impacts quality of life but its molecular mechanisms remain unclear.
- Mas-related G protein-coupled receptor A3 (MrgprA3) is a known itch-specific receptor, but its role in chronic itch is not fully understood.
- The acetone-ether-water (AEW) model provides a histamine-independent approach to studying chronic pruritus.
Purpose of the Study:
- To investigate the role of Mas-related G protein-coupled receptor A3 (MrgprA3) in chronic pruritus using the AEW model.
- To examine the expression levels and neuronal changes associated with MrgprA3 in a chronic itch condition.
Main Methods:
- Utilized behavioral tests to quantify scratching bouts in the AEW model.
- Performed immunostaining to assess MrgprA3 sensory fiber density in skin and neuron counts in dorsal root ganglia.
- Analyzed MrgprA3 mRNA levels to evaluate gene expression changes.
Main Results:
- Scratching behavior induced by chloroquine was significantly heightened under AEW conditions.
- A significant increase in MrgprA3 sensory fiber density was observed in AEW-treated skin.
- The number of MrgprA3 neurons in dorsal root ganglia and MrgprA3 mRNA levels were also significantly elevated post-AEW treatment.
Conclusions:
- MrgprA3 plays a critical role in the development and manifestation of chronic pruritus within the established AEW mouse model.
- The findings suggest MrgprA3 as a potential therapeutic target for managing chronic itch conditions.
