ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Activation of guanylate cyclase-C attenuates stretch responses and sensitization of mouse colorectal afferents.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Intestinal neuropod cell GUCY2C regulates visceral pain.The Journal of clinical investigation · 2023Article
- An anesthesia protocol for robust and repeatable measurement of behavioral visceromotor responses to colorectal distension in mice.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain.Trends in pharmacological sciences · 2022Review
- Toward Elucidating the Physiological Impacts of Residual Stresses in the Colorectum.Journal of biomechanical engineering · 2022Article
- Targeting Two-Pore-Domain Potassium Channels by Mechanical Stretch Instantaneously Modulates Action Potential Transmission in Mouse Sciatic Nerves.ACS chemical neuroscience · 2021Article
- The heterogeneous morphology of networked collagen in distal colon and rectum of mice quantified via nonlinear microscopy.Journal of the mechanical behavior of biomedical materials · 2021Article
- Computational Modeling of Mouse Colorectum Capturing Longitudinal and Through-thickness Biomechanical Heterogeneity.Journal of the mechanical behavior of biomedical materials · 2021Article
- Epithelial-Neuronal Communication in the Colon: Implications for Visceral Pain.Trends in neurosciences · 2020Review
- Mechanical Stimuli Affect Escherichia coli Heat-Stable Enterotoxin-Cyclic GMP Signaling in a Human Enteroid Intestine-Chip Model.Infection and immunity · 2020Article
- Load-bearing function of the colorectal submucosa and its relevance to visceral nociception elicited by mechanical stretch.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Immunizations with Enterotoxigenic Escherichia coli Heat-Stable Toxin Conjugates Engender Toxin-Neutralizing Antibodies in Mice That Also Cross-React with Guanylin and Uroguanylin.Infection and immunity · 2019Article
- Optical recording reveals topological distribution of functionally classified colorectal afferent neurons in intact lumbosacral DRG.Physiological reports · 2019Article
- Differential biomechanical properties of mouse distal colon and rectum innervated by the splanchnic and pelvic afferents.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Linaclotide Attenuates Visceral Organ Crosstalk: Role of Guanylate Cyclase-C Activation in Reversing Bladder-Colon Cross-Sensitization.The Journal of pharmacology and experimental therapeutics · 2018Article
- Clinical utility of plecanatide in the treatment of chronic idiopathic constipation.International journal of general medicine · 2018Review
- In Vitro Characterization of the Electrophysiological Properties of Colonic Afferent Fibers in Rats.Journal of visualized experiments : JoVE · 2017Article
- Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article.Anesthesiology and pain medicine · 2017Review
- Article
- Prolonged intestinal transit and diarrhea in patients with an activating GUCY2C mutation.PloS one · 2017Article
- Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Irritable bowel syndrome (IBS) is characterized by altered bowel habits, persistent pain and discomfort, and typically colorectal hypersensitivity. Linaclotide, a peripherally restricted 14 aa peptide approved for the treatment of IBS with constipation, relieves constipation and reduces IBS-associated pain in these patients presumably by activation of guanylate cyclase-C (GC-C), which stimulates production and release of cyclic guanosine monophosphate (cGMP) from intestinal epithelial cells. We investigated whether activation of GC-C by the endogenous agonist uroguanylin or the primary downstream effector of that activation, cGMP, directly modulates responses and sensitization of mechanosensitive colorectal primary afferents. The distal 2 cm of mouse colorectum with attached pelvic nerve was harvested and pinned flat mucosal side up for in vitro single-fiber recordings, and the encoding properties of mechanosensitive afferents (serosal, mucosal, muscular, and muscular-mucosal; M/M) to probing and circumferential stretch studied. Both cGMP (10-300 μM) and uroguanylin (1-1000 nM) applied directly to colorectal receptive endings significantly reduced responses of muscular and M/M afferents to stretch; serosal and mucosal afferents were not affected. Sensitized responses (i.e., increased responses to stretch) of muscular and M/M afferents were reversed by cGMP, returning responses to stretch to control. Blocking the transport of cGMP from colorectal epithelia by probenecid, a mechanism validated by studies in cultured intestinal T84 cells, abolished the inhibitory effect of uroguanylin on M/M afferents. These results suggest that GC-C agonists like linaclotide alleviate colorectal pain and hypersensitivity by dampening stretch-sensitive afferent mechanosensitivity and normalizing afferent sensitization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.