Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 contribute to the progression of colonic inflammation in dextran sulfate sodium-induced colitis in mice: Links to calcitonin gene-related peptide and substance P

Utsumi, Daichi; Matsumoto, Kenjiro; Tsukahara, Takuya; Amagase, Kikuko; Tominaga, Makoto; Kato, Shinichi

doi:10.1016/j.jphs.2017.12.012

Cited by 34 publications

(31 citation statements)

References 35 publications

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ DSS treatment of TRPA1 knockout mice has been found to increase the disease activity score and to elevate proinflammatory cytokine and neuropeptide concentrations in the colon 34 while other reports indicate that genetic deletion of TRPA1 has no effect 37 or protects from experimentally induced colitis 29,38 . Here we confirm that pharmacologic blockade of TRPA1 with HC-030031 and genetic deletion of TRPA1 has no overt effect on the severity of DSS-induced colitis in mice.…”

Section: Discussionmentioning

confidence: 99%

Transient receptor potential ankyrin 1 contributes to somatic pain hypersensitivity in experimental colitis

Jain

Materazzi

Logu

et al. 2020

Sci Rep

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Pain evoked by visceral inflammation is often 'referred' to the somatic level. Transient receptor potential ankyrin 1 (TRPA1) has been reported to contribute to visceral pain-like behavior in dextran sulfate sodium (DSS)-evoked colitis. However, the role of TRPA1 in somatic component of hypersensitivity due to visceral inflammation is unknown. The present study investigated the role of TRPA1 in colitis-evoked mechanical hypersensitivity at the somatic level. Colitis was induced in mice by adding DSS to drinking water for one week. Control and DSS-treated mice were tested for various parameters of colitis as well as mechanical pain sensitivity in abdominal and facial regions. DSS treatment caused mechanical hypersensitivity in the abdominal and facial skin. Pharmacological blockade or genetic deletion of TRPA1 prevented the colitis-associated mechanical hypersensitivity in the abdominal and facial skin areas although the severity of colitis remained unaltered. DSS treatment increased expression of TRPA1 mRNA in cultured dorsal root ganglion (DRG) neurons, but not trigeminal ganglion neurons, and selectively enhanced currents evoked by the TRPA1 agonist, allyl isothiocyanate, in cultured DRG neurons. Our findings indicate that the TRPA1 channel contributes to colitis-associated mechanical hypersensitivity in somatic tissues, an effect associated with upregulation of TRPA1 expression and responsiveness in DRG nociceptors.

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Section: Discussionmentioning

confidence: 99%

Transient receptor potential ankyrin 1 contributes to somatic pain hypersensitivity in experimental colitis

Jain

Materazzi

Logu

et al. 2020

Sci Rep

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“…Presently, we found a decrease in sympathetic nerve density (Figure 3), which is consistent with modestly decreased TH axons in gut submucosal arteries in 2,4,6-Trinitrobenzenesulfonic acid (TNBS) colitis 32 but in contrast to unchanged TH nerves in human submucosal arteries 33 and increased TH nerves in human MAs 34 with IBD. Sensory denervation exacerbates colitis in female oxazolone-induced 35 , TRPV1 -/-Dextran Sulfate Sodium (DSS)induced 36 mouse models and some TNBS-induced rat models 37, 38 but improves colitis in a different TNBS rat model 39 and DSS and TNBS mouse models 40 . We report increased SP and unchanged CGRP nerve density on MAs with IBD ( Figure 3), similar to reports in human submucosal arteries 34 .…”

Section: Discussionmentioning

confidence: 99%

Altered substance P signaling underlies perivascular sensory nerve dysfunction in inflammatory bowel disease

Norton

Grunz-Borgmann

Hart

et al. 2020

Preprint

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Objective: Inflammatory Bowel Disease (IBD) is associated with cardiovascular disease risk and impaired intestinal blood flow, but the functional role of perivascular nerves that control vasomotor function of mesenteric arteries (MAs) perfusing the intestine is unknown in IBD. Because perivascular sensory nerves and their transmitters calcitonin gene-related peptide (CGRP) and substance P (SP) are important mediators of both vasodilation and inflammatory responses, our objective was to identify IBD-related deficits in perivascular sensory nerve function and vascular neurotransmitter signaling.Approach and Results: In MAs from an IL-10 -/mouse model, we found that IBD significantly impairs EFS-mediated sensory vasodilation and sensory inhibition of sympathetic vasoconstriction, despite decreased sympathetic nerve density and vasoconstriction. The MA content and EFS-mediated release of both CGRP and SP are slightly decreased with IBD, but IBD has different effects on each transmitter. CGRP nerve density, receptor expression, hyperpolarization and vasodilation are preserved with IBD. In contrast, SP nerve density and receptor expression are increased, and SP hyperpolarization and vasodilation are impaired with IBD. A critical finding is that blocking neurokinin 1 (SP) receptors restored EFS-mediated sensory vasodilation and enhanced CGRP-mediated vasodilation in MAs from IBD but not Control mice.Conclusions: An aberrant role for the perivascular sensory neurotransmitter SP and its downstream signaling in MAs underlies vascular dysfunction with IBD. With IBD, SP signaling impedes CGRP-mediated sensory vasodilation, contributing to impaired blood flow. Substance P and NK1 receptors may represent an important target for treating vascular dysfunction in IBD.

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“…Afferent sensory C neuronal fibers play an important role in regulation of gastric microcirculation and therefore in the maintenance of gastric mucosal integrity by the mechanism involving release of vasoactive CGRP due to activation of TRPV1 [ 6 , 7 , 11 , 13 ]. Interestingly, endogenous gaseous mediators NO, H 2 S, and CO have been shown to increase GBF and prevent gastric mucosa from the formation of acute gastric mucosal lesions induced by intragastric application of aspirin, ethanol, strong acid and bases, or exposure of experimental animals to cold stress [ 8 , 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions

Magierowska

Wójcik

Chmura

et al. 2018

IJMS

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Carbon monoxide (CO) has been reported to contribute to the maintenance of gastric mucosal integrity, gastroprotection, and ulcer healing. However, involvement of transient receptor potential vanilloid receptor type 1 (TRPV1) located on afferent sensory fibers endings and sensory neuropeptide calcitonin gene-related peptide (CGRP) in CO-mediated gastroprotection against ethanol-induced gastric damage has not been explored. Male Wistar rats with and without denervation of afferent sensory neurons induced by capsaicin (total dose 125 mg/kg within 3 days) were pretreated with vehicle, CO donor tricarbonyldichlororuthenium (II) dimer (CORM-2, 5 mg/kg i.g.), administered alone or with CGRP-α (10 μg/kg i.p.) or TRPV1 antagonist capsazepine (5 mg/kg i.g.), followed 30 min later by intragastric (i.g.) administration of 75% ethanol. The area of gastric damage and gastric blood flow (GBF) were assessed planimetrically and by laser flowmetry, respectively. Microscopic evaluation of ethanol-induced gastric lesions was performed after haematoxylin/eosin (H&E) or alcian blue/periodic acid-Schiff/alcian blue (AB/PAS) staining. Gastric mucosal mRNA fold change for heme oxygenase (HMOX)-1, HMOX-2, CGRP-α, CGRP-β, inducible nitric oxide synthase (iNOS), endothelial (e)NOS, neuronal (n)NOS, cyclooxygenase (COX)-1, COX-2, and protein expression for HMOX-1 and TRPV1 was determined by real-time PCR or Western blot, respectively. Pretreatment with CORM-2 combined or not with CGRP reduced ethanol-induced gastric lesions and elevated GBF. Capsaicin-denervation or co-treatment with capsazepine or CGRP and CORM-2 in capsaicin-denervated animals failed to affect these beneficial effects of CO donor. In rats with intact sensory nerves, CORM-2 increased gastric mRNA level for HMOX-1 and CGRP-α. In capsaicin-denervated rats, CORM-2 increased eNOS mRNA fold change and TRPV1 protein expression while capsaicin denervation itself decreased HMOX-1 protein expression and eNOS mRNA level. We conclude that CO prevents gastric mucosa from ethanol-induced lesions due to activation of TRPV1/CGRP-α system and accompanying increase in gastric microcirculation but independently on afferent sensory nerve activity despite the stimulation of TRPV1 protein and CGRP-α mRNA expression.

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Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 contribute to the progression of colonic inflammation in dextran sulfate sodium-induced colitis in mice: Links to calcitonin gene-related peptide and substance P

Cited by 34 publications

References 35 publications

Transient receptor potential ankyrin 1 contributes to somatic pain hypersensitivity in experimental colitis

Transient receptor potential ankyrin 1 contributes to somatic pain hypersensitivity in experimental colitis

Altered substance P signaling underlies perivascular sensory nerve dysfunction in inflammatory bowel disease

Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions

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