Functional neuromuscular impairment in severe intestinal dysmotility

Gallego, Diana; Malagelada, Carolina; Accarino, Anna; Gori, Alessandra; Malagelada, Juan R.; Azpiroz, Fernando; Giorgio, Roberto De; Jiménez, Marcel

doi:10.1111/nmo.13458

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…In the present study, we show that also HNO, released by the donor Angeli's salt, elicits a relaxation of both circular and longitudinal muscle strips from the rat ileum or colon (Figures 1-3) as do NO and H 2 S in different species including rat (Tam and Hillier, 1992;Boeckxstaens et al, 1993;Stark et al, 1993;Teague et al, 2002). This relaxation reaches a maximum within 3 min after application of the donor, which also matches with the profile of NO or H 2 S in their relaxing property (Gallego et al, 2008(Gallego et al, , 2018. Both the basal tone and the frequency of phasic contractions are reduced by the signaling molecule.…”

Section: Discussionsupporting

confidence: 81%

Mechanisms Associated to Nitroxyl (HNO)-Induced Relaxation in the Intestinal Smooth Muscle

2020

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Section: Discussionsupporting

confidence: 81%

Mechanisms Associated to Nitroxyl (HNO)-Induced Relaxation in the Intestinal Smooth Muscle

2020

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“…Organ bath tissue contractility testing does hold promise for clinical utility to better understand and classify intestinal motility disorders. As an in vitro technique used mainly in animal experiments, its use has been integrated into clinical practice to accurately characterize the pathophysiology underlying GI motility disorders and assess pharmacological responses (24,25). In vitro, tissue-based approaches also allow for the manipulation of cellular components using genetic tools or the development of regenerative medicine strategies (eg, 3D organoid models, organ-on-a-chip).…”

Section: Improved Investigation Of Motility Disordersmentioning

confidence: 99%

Pediatric Neurogastroenterology and Motility: Moving Rapidly Into the Future

Chanpong

Thapar

2023

Journal of Pediatric Gastroenterology &Amp; Nutrition

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The field of pediatric neurogastroenterology and motility encompasses some of the most common and severe gastrointestinal (GI) disorders that affect children. GI motility disorders remain, in general, poorly understood, variably diagnosed, and inadequately treated. Although the field progressed relatively slowly over the last decades, the coming years will, no doubt, see it move into a prolific and dynamic era. With this review, we look forward to this brighter future for the field and highlight emerging areas that show promise and deserve focus in the coming years. This includes the role of early life programming and insult of the enteric neuromusculature as a key determinant of motility diseases and factors that are likely to be relevant in disease etiopathogenesis. We discuss several recent and futuristic developments and advancements in investigative and diagnostic tools as well as novel approaches that have been introduced in the management of GI motility disorders. These include targeted and personalized medicine in both pharmacological and multidisciplinary approaches as well as the emerging therapeutic options such as bioelectrical neuromodulation and regenerative medicine.

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“…Accordingly, NO has been associated with receptive relaxation whereas purine‐mediated relaxations are transient and possibly associated with the relaxation needed for propulsion . Recently, impairment of purinergic neuromuscular transmission has been associated with several diseases including animal models of inflammation and human enteric dysmotility and pseudo obstruction …”

Section: Introductionmentioning

confidence: 99%

The asymmetric innervation of the circular and longitudinal muscle of the mouse colon differently modulates myogenic slow phasic contractions

Traserra

Villarte

Traini

et al. 2019

Neurogastroenterology Motil

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Background Neuromuscular transmission has been extensively studied in the circular layer of the mouse colon where a co‐transmission of purines acting on P2Y1 receptors and NO has been previously described. However, the corresponding mechanisms in the longitudinal layer are less known. Methods Electrophysiological and myography techniques were used to evaluate spontaneous phasic contractions (SPC) and neural‐mediated responses in the proximal, mid, and distal colon devoid of CD1 mice. Immunohistochemistry against c‐kit and PDGFRα was performed in each colonic segment. Key Results SPC were recorded in both muscle layers at a similar frequency being about four contractions per minute (c.p.m.) in the proximal and distal colon compared to the mid colon (2 c.p.m.). In non‐adrenergic, non‐cholinergic conditions, L‐NNA (1 mmol/L) increased contractility in the circular but not in the longitudinal layer. In the longitudinal muscle, both electrophysiological and mechanical neural‐mediated inhibitory responses were L‐NNA and ODQ (10 µmol/L) sensitive. NaNP (1 µmol/L) caused cessation of SPC and the response was blocked by ODQ. Neither ADPßS (10 µmol/L) nor CYPPA (10 µmol/L), which both targeted the purinergic pathway, altered longitudinal contractions. PDGFRα + cells were located in both muscle layers and were more numerous compared with cKit + cells, which both formed a heterologous cellular network. A decreasing gradient of the PDGFRα labeling was observed along the colon. Conclusion An inhibitory neural tone was absent in the longitudinal layer and neuronal inhibitory responses were mainly nitrergic. Despite the presence of PDGFRα + cells, purinergic responses were absent. Post‐junctional pathways located in different cell types might be responsible for neurotransmitter transduction.

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Functional neuromuscular impairment in severe intestinal dysmotility

Cited by 5 publications

References 33 publications

Mechanisms Associated to Nitroxyl (HNO)-Induced Relaxation in the Intestinal Smooth Muscle

Mechanisms Associated to Nitroxyl (HNO)-Induced Relaxation in the Intestinal Smooth Muscle

Pediatric Neurogastroenterology and Motility: Moving Rapidly Into the Future

The asymmetric innervation of the circular and longitudinal muscle of the mouse colon differently modulates myogenic slow phasic contractions

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