Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat experimental colitis

Silva, Marcos Vinícius da; Marosti, Aline Rosa; Mendes, Cristina Eusébio; Palombit, Kelly; Castelucci, Patrícia

doi:10.1016/j.acthis.2017.05.001

Cited by 25 publications

(16 citation statements)

References 84 publications

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“…P2X7R-expressing enteric neurons are differentially affected in UC based on their chemical codes ( da Silva et al, 2015 ). In a later paper, it was shown that UC affected secretory and vasodilatory neurons, enteric sensory neurons and enteric glia of the submucosal plexus expressing P2X7R ( da Silva et al, 2017 ). The P2X7R antagonist, A438079, down-regulated the production of proinflammatory cytokines and attenuated murine colitis, indicating that P2X7R mediate inflammatory responses during UC ( Wan P. et al, 2016 ).…”

Section: Gut Disordersmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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Section: Gut Disordersmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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“…Most of the studies involving the ENS have demonstrated a decrease in the number of cells that are immunoreactive to the P2X7 receptor in the submucosal and myenteric plexus following ischemia/reperfusion in the ilea of rats [ 127 , 131 , 132 ] and intestinal inflammation in rats[ 128 - 130 , 133 ], mice, and humans[ 19 ]. Moreover, the alteration of these same neurons was observed in the ENS of the large intestine of rats subjected to undernourishment protein and renutrition[ 121 ].…”

Section: The Purinergic Receptorsmentioning

confidence: 99%

Enteric nervous system and inflammatory bowel diseases: Correlated impacts and therapeutic approaches through the P2X7 receptor

Magalhães¹,

Castelucci²

2021

WJG

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The enteric nervous system (ENS) consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses, which can be negatively affected by Crohn’s disease and ulcerative colitis - inflammatory bowel diseases (IBDs). IBDs are complex and multifactorial disorders characterized by chronic and recurrent inflammation of the intestine, and the symptoms of IBDs may include abdominal pain, diarrhea, rectal bleeding, and weight loss. The P2X7 receptor has become a promising therapeutic target for IBDs, especially owing to its wide expression and, in the case of other purinergic receptors, in both human and model animal enteric cells. However, little is known about the actual involvement between the activation of the P2X7 receptor and the cascade of subsequent events and how all these activities associated with chemical signals interfere with the functionality of the affected or treated intestine. In this review, an integrated view is provided, correlating the structural organization of the ENS and the effects of IBDs, focusing on cellular constituents and how therapeutic approaches through the P2X7 receptor can assist in both protection from damage and tissue preservation.

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“…According to reports in the literature, CB belongs to the family of calcium-binding proteins. Studies have shown that CB is mainly expressed in primary sensory afferent neurons and participates in sensory information transmission in the gastrointestinal tract [36,39,41,42]. CGRP, an important neurotransmitter, is mainly released by submucosal plexus cells that transmit various mechanical and chemical irritative sensory information in the gastrointestinal tract [39,43,44].…”

Section: Distribution Of Mor and P2y 1 Receptor In Rat Colonic Submucosal Plexusmentioning

confidence: 99%

The P2Y1 Receptor in the Colonic Submucosa of Rats and Its Correlation with Opioid-Induced Constipation

Zhao

Ren

Li³

et al. 2021

Preprint

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Aims: To explore the expression changes of P2Y1 in the distal colonic submucosa of opioid induced constipation (OIC) rats and its correlation with the occurrence of OIC. Methods: OIC model was generated by intraperitoneal injection of loperamide hydrochloride, a selective agonist of the μ-opioid receptor (MOR). Seven days later, the model was assessing by detecting the fecal traits and calculating the fecal water cotent. The distribution of MOR-containing neurons and P2Y1-containing neurons in colonic submucosal plexus of rat were demonstrated by immunofluorescence histochemistry. Western Blot was used to evaluate the expression changes of MOR, P2Y1 and ATP synthase subunit beta (ATPB) in colonic submucosa, while the RT-PCR analysis was performed to determine the relative mRNA expression of MOR, P2Y1 and ATPB. Results: After seven days, the feces of OIC rats had an appearance of like sausage-shaped pieces, and the fecal water content, stool weight of OIC rats were decreased. Immunofluorescence histochemistry showed the co-expression of MOR and ATPB, P2Y1 and calbindin (CB) in the nerve cells of distal colonic submucosal plexus. RT-PCR showed that MOR mRNA levels were significantly increased in the distal colonic submucosa of OIC rats, while the mRNA levels of P2Y1 were decreased. Western blot results showed that MOR protein expression was increased, and the P2Y1 protein expression was significantly decreased in the distal colonic submucosa of OIC rats.Conclusion: P2Y1 is associated with the occurrence of OIC in rats, and the expression of MOR and P2Y1 and OIC are correlated with each other.

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Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat experimental colitis

Cited by 25 publications

References 84 publications

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling: Therapeutic Developments

Enteric nervous system and inflammatory bowel diseases: Correlated impacts and therapeutic approaches through the P2X7 receptor

The P2Y1 Receptor in the Colonic Submucosa of Rats and Its Correlation with Opioid-Induced Constipation

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