Activation of protease‐activated receptor‐4 inhibits the intrinsic excitability of colonic dorsal root ganglia neurons
Abstract
Abstract The antinociceptive mechanism underlying protease‐activated receptor‐4 (PAR 4) activation was studied in Fast Blue‐labelled dorsal root ganglia (DRG) neurons from mouse colon which expressed transcript for PAR 4. Whole cell perforated patch clamp recordings were obtained from these neurons and the effects on neuronal excitability of PAR 4 activating peptides (AP) and reverse peptides (RP) were examined. A 3‐min application of PAR 4‐AP (100 μ mol L−1) markedly suppressed the number of action potential discharged at twice rheobase for up to 60 min. PAR 4‐RP had no effect. PAR 4 application suppresses the excitatory effects of PAR 2. These findings demonstrated that activation of PAR 4 on colonic DRG neurons suppresses their excitability, suggesting these receptors could provide important targets for modifying pain in colonic GI disorders such as IBS and IBD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Activation of PAR-4 has opposite effects on nociceptor activation to PAR-2 activation in rodents.
“Importantly, activation of PAR-4 has opposite effects on nociceptor activation to PAR-2 activation in rodents.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [157]
PAR-4 activation suppresses the excitability of colonic nociceptors in vitro and in vivo.
“PAR-4 activation suppresses the excitability of colonic nociceptors in vitro,157 and in vivo.158”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [157]
Cites
Protease-Activated Receptors: Contribution to Physiology and Disease
Ossovskaya, V., & Bunnett, N. W. (2004) · Physiological Reviews · doi:10.1152/physrev.00028.2003 · Cited by 1,079 · see citing works
Beyak, M. J., Ramji, N., Krol, K. M., Kawaja, M. D., & Vanner, S. J. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00154.2004 · Cited by 150 · see citing works
Self-citationProtease‐activated receptor‐4: a novel mechanism of inflammatory pain modulation
Asfaha, S., Cénac, N., Houle, S., Altier, C., Papez, M. D., Nguyen, C., Steinhoff, M. S., Chapman, K., Zamponi, G. W., & Vergnolle, N. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706975 · Cited by 143 · see citing works
Protease-Activated Receptors: How Proteases Signal to Cells to Cause Inflammation and Pain
Bunnett, N. W. (2006) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-2006-939553 · Cited by 131 · see citing works
Augé, C., Balz‐hara, D., Steinhoff, M., Vergnolle, N., & Cenac, N. (2009) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2009.01310.x · Cited by 99 · see citing works
D’Andrea, M. R., Saban, M. R., Nguyen, N.-B., Andrade‐Gordon, P., & Saban, R. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63886-2 · Cited by 93 · see citing works
Kayssi, A., Amadesi, S., Bautista, F., Bunnett, N. W., & Vanner, S. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2006.126599 · Cited by 64 · see citing works
Self-citationProtease Signaling to G Protein-Coupled Receptors: Implications for Inflammation and Pain
Dale, C. S., & Vergnolle, N. (2008) · Journal of Receptors and Signal Transduction · doi:10.1080/10799890801941913 · Cited by 41 · see citing works
King, D. E., MacLeod, R., & Vanner, S. J. (2009) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2009.01279.x · Cited by 37 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Structure, function and pathophysiology of protease activated receptors
Adams, M. N., Ramachandran, R., Yau, M.-K., Suen, J. Y., Fairlie, D. P., Hollenberg, M. D., & Hooper, J. D. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.01.003 · Cited by 370 · see citing works
Protease-activated receptors in health and disease
Peach, C. J., Edgington-Mitchell, L. E., Bunnett, N. W., & Schmidt, B. L. (2023) · Physiological Reviews · doi:10.1152/physrev.00044.2021 · Cited by 116 · see citing works
Valdez-Morales, E. E., Overington, J., Guerrero-Alba, R., Ochoa-Cortes, F., Ibeakanma, C. O., Spreadbury, I., Bunnett, N. W., Beyak, M., & Vanner, S. J. (2013) · American Journal of Gastroenterology · doi:10.1038/ajg.2013.241 · Cited by 107 · see citing works
Self-citationThe emerging roles of bacterial proteases in intestinal diseases
Caminero, A., Guzman, M., Libertucci, J., & Lomax, A. E. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2181922 · Cited by 92 · see citing works
Protease-Mediated Suppression of DRG Neuron Excitability by Commensal Bacteria
Sessenwein, J. L., Baker, C. C., Pradhananga, S., Maitland, M. E., Petrof, E. O., Allen-Vercoe, E., Noordhof, C., Reed, D. E., Vanner, S. J., & Lomax, A. E. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.1672-17.2017 · Cited by 58 · see citing works
Self-citationCeuleers, H., Hanning, N., Heirbaut, J., Van Remoortel, S., Joossens, J., Van Der Veken, P., Francque, S. M., De bruyn, M., Lambeir, A., De Man, J. G., et al. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14396 · Cited by 49 · see citing works
- Authors
- Karanjia, R., Spreadbury, I., Bautista‐cruz, F., Tsang, M. E., & Vanner, S.
- Affiliations
- Queen's University (CA)
- Corresponding author
- Vanner, S.
- Venue
- Neurogastroenterology & Motility
- Publisher
- Wiley
- Published
- 2009-10-02
- Volume
- 21
- Issue
- 11
- Pages
- 1218-1221
- ISSN
- 1350-1925 (ISSN-L)
- 1365-2982
- OpenAlex
- W2048493600
- Cited by
- 38
- References
- 9
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 2 · 2012: 4
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurogastroenterology & Motility (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- PAR4, dorsal root ganglion neurons, colonic pain, neuronal excitability, antinociception, PAR2, inflammatory bowel disease, irritable bowel syndrome, gastrointestinal pain
- MeSH terms
- Action Potentials, Animals, Colon, Female, Ganglia, Spinal, Male, Neurons, Afferent, Pain, Peptides, Receptors, Thrombin, Patch-Clamp Techniques, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
