Mas‐related G protein‐coupled receptor C11 (Mrgprc11) induces visceral hypersensitivity in the mouse colon: A novel target in gut nociception?

2019 ◽  
Vol 31 (8) ◽  
Author(s):  
Samuel Van Remoortel ◽  
Hannah Ceuleers ◽  
Rohit Arora ◽  
Luc Van Nassauw ◽  
Joris G. De Man ◽  
...  
Keyword(s):  
G Protein ◽  
Visceral Hypersensitivity ◽  
G Protein Coupled Receptor ◽  
Mouse Colon ◽  
Novel Target ◽  
G Protein Coupled

scholarly journals Phosphoproteomic Analysis of the Amygdala Response to Adolescent Glucocorticoid Exposure Reveals G-Protein Coupled Receptor Kinase 2 as a Target for Reducing Motivation for Alcohol

Proteomes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 41 ◽  
Author(s):  
Megan Bertholomey ◽  
Kathryn Stone ◽  
TuKiet Lam ◽  
Seojin Bang ◽  
Wei Wu ◽  
...  
Keyword(s):  
G Protein ◽  
Life Stress ◽  
Early Life Stress ◽  
Progressive Ratio ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Self Administration ◽  
Amygdala Response ◽  
Novel Target ◽  
G Protein Coupled

Early life stress is associated with risk for developing alcohol use disorders (AUDs) in adulthood. Though the neurobiological mechanisms underlying this vulnerability are not well understood, evidence suggests that aberrant glucocorticoid and noradrenergic system functioning play a role. The present study investigated the long-term consequences of chronic exposure to elevated glucocorticoids during adolescence on the risk of increased alcohol-motivated behavior, and on amygdalar function in adulthood. A discovery-based analysis of the amygdalar phosphoproteome using mass spectrometry was employed, to identify changes in function. Adolescent corticosterone (CORT) exposure increased alcohol, but not sucrose, self-administration, and enhanced stress-induced reinstatement with yohimbine in adulthood. Phosphoproteomic analysis indicated that the amygdala phosphoproteome was significantly altered by adolescent CORT exposure, generating a list of potential novel mechanisms involved in the risk of alcohol drinking. In particular, increased phosphorylation at serines 296–299 on the α2A adrenergic receptor (α2AAR), mediated by the G-protein coupled receptor kinase 2 (GRK2), was evident after adolescent CORT exposure. We found that intra-amygdala infusion of a peptidergic GRK2 inhibitor reduced alcohol seeking, as measured by progressive ratio and stress reinstatement tests, and induced by the α2AAR antagonist yohimbine. These results suggest that GRK2 represents a novel target for treating stress-induced motivation for alcohol which may counteract alterations in brain function induced by adolescent stress exposure.

scholarly journals 5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein–coupled receptor D

2018 ◽  
Vol 11 (561) ◽  
pp. eaal2171 ◽  
Author(s):  
Tereza Bautzova ◽  
James R. F. Hockley ◽  
Teresa Perez-Berezo ◽  
Julien Pujo ◽  
Michael M. Tranter ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
G Protein ◽  
Visceral Hypersensitivity ◽  
Mechanical Stimuli ◽  
Drg Neurons ◽  
G Protein Coupled Receptor ◽  
Irritable Bowel ◽  
Nerve Recordings ◽  
G Protein Coupled

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-oxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-oxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-oxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca2+imaging of dorsal root ganglion (DRG) neurons. We showed that 5-oxoETE selectively stimulated nonpeptidergic, isolectin B4 (IB4)–positive DRG neurons through a phospholipase C (PLC)– and pertussis toxin–dependent mechanism, suggesting that the effect was mediated by a G protein–coupled receptor (GPCR). The MAS-related GPCR D (Mrgprd) was found in mouse colonic DRG afferents and was identified as being implicated in the noxious effects of 5-oxoETE. Together, these data suggest that 5-oxoETE, a potential biomarker of IBS-C, induces somatic and visceral hyperalgesia without inflammation in an Mrgprd-dependent manner. Thus, 5-oxoETE may play a pivotal role in the abdominal pain associated with IBS-C.

Vanadium compounds cause activation of G protein-coupled receptor signaling

2020 ◽  
Author(s):  
Debbie C. Crans ◽  
Duaa Althumairy ◽  
Heide Murakami ◽  
B. George Barisas ◽  
Deborah Roess
Keyword(s):  
G Protein ◽  
Receptor Signaling ◽  
G Protein Coupled Receptor ◽  
Vanadium Compounds ◽  
G Protein Coupled
Sign in / Sign up

Export Citation Format

Share Document