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Mas-related G protein-coupled receptor C11 (Mrgprc11) induces visceral hypersensitivity in the mouse colon: A novel target in gut nociception?
Neurogastroenterol Motil 2019; 31(8):1-12NM

Abstract

BACKGROUND

Visceral hypersensitivity, an important cause of abdominal pain in disorders such as IBD and IBS, presents with a poorly understood pathophysiology and limited treatment options. Several members of the Mas-related G protein-coupled receptor family (Mrgprs) have become promising targets in pain research. The potential link between the murine Mrgpr C11 (Mrgprc11) and gut nociception is currently uninvestigated. Therefore, we explored the expression and functional role of Mrgprc11 in the gut nociceptive innervation.

METHODS

Mrgprc11 expression was evaluated in DRG neurons innervating the mouse colon using in situ hybridization and immunohistochemistry. Visceromotor responses to colorectal distension (CRD) assessed the effect of the Mrgprc11 agonist, BAM(8-22), on colonic pain sensitivity in healthy mice. Moreover, we determined pERK1/2-immunoreactivity in the thoracolumbar spinal cord after noxious CRD. Finally, from a translational point of view, we looked for expression of the human counterpart of Mrgprc11, MRGPRX1, in human thoracolumbar DRGs.

KEY RESULTS

In situ hybridization and immunohistochemistry revealed Mrgprc11 expression in colonic DRG neurons. Intracolonic administration of BAM(8-22) significantly increased colonic pain sensitivity in an Mrgprc11-dependent manner, and led to a significantly increased degree of neuronal activation in the splanchnic spinal cord upon noxious stimulation. Furthermore, MRGPRX1 expression was also detected in human thoracolumbar DRG neurons. CONCLUSIONS & INFERENCES: Our findings established a novel function for Mrgprc11 in the gut nociceptive innervation and propose the receptor as a new player in visceral hypersensitivity. Given the presence of MRGPRX1 in human DRG neurons, our study warrants future research on its therapeutic potential in abdominal pain disorders.

Authors+Show Affiliations

Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.Laboratory of Human Anatomy and Embryology, Division ASTARC, University of Antwerp, Antwerp, Belgium.Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31119828

Citation

Van Remoortel, Samuel, et al. "Mas-related G Protein-coupled Receptor C11 (Mrgprc11) Induces Visceral Hypersensitivity in the Mouse Colon: a Novel Target in Gut Nociception?" Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 31, no. 8, 2019, pp. 1-12.
Van Remoortel S, Ceuleers H, Arora R, et al. Mas-related G protein-coupled receptor C11 (Mrgprc11) induces visceral hypersensitivity in the mouse colon: A novel target in gut nociception? Neurogastroenterol Motil. 2019;31(8):1-12.
Van Remoortel, S., Ceuleers, H., Arora, R., Van Nassauw, L., De Man, J. G., Buckinx, R., ... Timmermans, J. P. (2019). Mas-related G protein-coupled receptor C11 (Mrgprc11) induces visceral hypersensitivity in the mouse colon: A novel target in gut nociception? Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 31(8), pp. 1-12. doi:10.1111/nmo.13623.
Van Remoortel S, et al. Mas-related G Protein-coupled Receptor C11 (Mrgprc11) Induces Visceral Hypersensitivity in the Mouse Colon: a Novel Target in Gut Nociception. Neurogastroenterol Motil. 2019;31(8):1-12. PubMed PMID: 31119828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mas-related G protein-coupled receptor C11 (Mrgprc11) induces visceral hypersensitivity in the mouse colon: A novel target in gut nociception? AU - Van Remoortel,Samuel, AU - Ceuleers,Hannah, AU - Arora,Rohit, AU - Van Nassauw,Luc, AU - De Man,Joris G, AU - Buckinx,Roeland, AU - De Winter,Benedicte Y, AU - Timmermans,Jean-Pierre, Y1 - 2019/05/22/ PY - 2019/02/26/received PY - 2019/04/24/revised PY - 2019/04/26/accepted PY - 2019/5/24/pubmed PY - 2019/5/24/medline PY - 2019/5/24/entrez KW - MRGPRX1 KW - Mas-related G protein-coupled receptors KW - Mrgprc11 KW - nociception KW - visceral hypersensitivity SP - 1 EP - 12 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol. Motil. VL - 31 IS - 8 N2 - BACKGROUND: Visceral hypersensitivity, an important cause of abdominal pain in disorders such as IBD and IBS, presents with a poorly understood pathophysiology and limited treatment options. Several members of the Mas-related G protein-coupled receptor family (Mrgprs) have become promising targets in pain research. The potential link between the murine Mrgpr C11 (Mrgprc11) and gut nociception is currently uninvestigated. Therefore, we explored the expression and functional role of Mrgprc11 in the gut nociceptive innervation. METHODS: Mrgprc11 expression was evaluated in DRG neurons innervating the mouse colon using in situ hybridization and immunohistochemistry. Visceromotor responses to colorectal distension (CRD) assessed the effect of the Mrgprc11 agonist, BAM(8-22), on colonic pain sensitivity in healthy mice. Moreover, we determined pERK1/2-immunoreactivity in the thoracolumbar spinal cord after noxious CRD. Finally, from a translational point of view, we looked for expression of the human counterpart of Mrgprc11, MRGPRX1, in human thoracolumbar DRGs. KEY RESULTS: In situ hybridization and immunohistochemistry revealed Mrgprc11 expression in colonic DRG neurons. Intracolonic administration of BAM(8-22) significantly increased colonic pain sensitivity in an Mrgprc11-dependent manner, and led to a significantly increased degree of neuronal activation in the splanchnic spinal cord upon noxious stimulation. Furthermore, MRGPRX1 expression was also detected in human thoracolumbar DRG neurons. CONCLUSIONS & INFERENCES: Our findings established a novel function for Mrgprc11 in the gut nociceptive innervation and propose the receptor as a new player in visceral hypersensitivity. Given the presence of MRGPRX1 in human DRG neurons, our study warrants future research on its therapeutic potential in abdominal pain disorders. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/31119828/Mas-related_G_protein-coupled_receptor_C11_(Mrgprc11)_induces_visceral_hypersensitivity_in_the_mouse_colon:_A_novel_target_in_gut_nociception L2 - https://doi.org/10.1111/nmo.13623 DB - PRIME DP - Unbound Medicine ER -