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Potentiation of TRPV4 signalling by histamine and serotonin: an important mechanism for visceral hypersensitivity.
Gut. 2010 Apr; 59(4):481-8.Gut

Abstract

BACKGROUND

Although evidence points to a role for histamine and serotonin in visceral hypersensitivity, activation of calcium channels such as transient receptor potential vanilloid 4 (TRPV4) also causes visceral hypersensitivity. We hypothesised that TRPV4 is important for the generation of hypersensitivity, mediating histamine- and serotonin-induced visceral hypersensitivity.

METHODS

In response to histamine, serotonin and/or TRPV4 agonist (4alphaPDD), calcium signals and TRPV4 localisation studies were performed on dorsal root ganglia (DRG) neurons projecting from the colon. To evaluate visceral nociception, colorectal distension (CRD) was performed in mice treated with serotonin or histamine and with 4alphaPDD. Intrathecal injection of TRPV4 silencer RNA (SiRNA) or mismatch SiRNA was used to target TRPV4 expression.

RESULTS

Pre-exposure of DRG neurons projecting from the colon, to histamine or serotonin, increased Ca(2+) responses induced by 4alphaPDD by a protein kinase C (PKC), phospholipase Cbeta (PLCbeta), mitogen-activated protein kinase kinase (MAPKK) and phospholipase A(2) (PLA(2))-dependent mechanisms. Serotonin or histamine treatments enhanced TRPV4 expression at the plasma membrane by a MAPKK mechanism. Hypersensitivity induced by serotonin or histamine were both significantly inhibited by TRPV4 SiRNA intrathecal injection. Administration of sub-nociceptive doses of serotonin or histamine potentiated 4alphaPDD-induced hypersensitivity in response to CRD.

CONCLUSIONS

Serotonin and histamine sensitise TRPV4 response to 4alphaPDD both in vivo (increased visceral hypersensitivity) and in vitro, in sensory neurons, by a PKC, PLA(2), PLCbeta and MAPKK-dependent mechanism. Serotonin and histamine caused a MAPKK-dependent increase in TRPV4 expression in colonic sensory neurons plasma membranes. Further, histamine- or serotonin-mediated visceral hypersensitivity depend on TRPV4 expression in sensory neurons. TRPV4 appears as a common mechanism to several known mediators of visceral hypersensitivity.

Authors+Show Affiliations

NSERM U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France. nathalie.vergnolle@inserm.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20332520

Citation

Cenac, Nicolas, et al. "Potentiation of TRPV4 Signalling By Histamine and Serotonin: an Important Mechanism for Visceral Hypersensitivity." Gut, vol. 59, no. 4, 2010, pp. 481-8.
Cenac N, Altier C, Motta JP, et al. Potentiation of TRPV4 signalling by histamine and serotonin: an important mechanism for visceral hypersensitivity. Gut. 2010;59(4):481-8.
Cenac, N., Altier, C., Motta, J. P., d'Aldebert, E., Galeano, S., Zamponi, G. W., & Vergnolle, N. (2010). Potentiation of TRPV4 signalling by histamine and serotonin: an important mechanism for visceral hypersensitivity. Gut, 59(4), 481-8. https://doi.org/10.1136/gut.2009.192567
Cenac N, et al. Potentiation of TRPV4 Signalling By Histamine and Serotonin: an Important Mechanism for Visceral Hypersensitivity. Gut. 2010;59(4):481-8. PubMed PMID: 20332520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potentiation of TRPV4 signalling by histamine and serotonin: an important mechanism for visceral hypersensitivity. AU - Cenac,Nicolas, AU - Altier,Christophe, AU - Motta,Jean-Paul, AU - d'Aldebert,Emilie, AU - Galeano,Sophie, AU - Zamponi,Gerald W, AU - Vergnolle,Nathalie, PY - 2010/3/25/entrez PY - 2010/3/25/pubmed PY - 2010/4/28/medline SP - 481 EP - 8 JF - Gut JO - Gut VL - 59 IS - 4 N2 - BACKGROUND: Although evidence points to a role for histamine and serotonin in visceral hypersensitivity, activation of calcium channels such as transient receptor potential vanilloid 4 (TRPV4) also causes visceral hypersensitivity. We hypothesised that TRPV4 is important for the generation of hypersensitivity, mediating histamine- and serotonin-induced visceral hypersensitivity. METHODS: In response to histamine, serotonin and/or TRPV4 agonist (4alphaPDD), calcium signals and TRPV4 localisation studies were performed on dorsal root ganglia (DRG) neurons projecting from the colon. To evaluate visceral nociception, colorectal distension (CRD) was performed in mice treated with serotonin or histamine and with 4alphaPDD. Intrathecal injection of TRPV4 silencer RNA (SiRNA) or mismatch SiRNA was used to target TRPV4 expression. RESULTS: Pre-exposure of DRG neurons projecting from the colon, to histamine or serotonin, increased Ca(2+) responses induced by 4alphaPDD by a protein kinase C (PKC), phospholipase Cbeta (PLCbeta), mitogen-activated protein kinase kinase (MAPKK) and phospholipase A(2) (PLA(2))-dependent mechanisms. Serotonin or histamine treatments enhanced TRPV4 expression at the plasma membrane by a MAPKK mechanism. Hypersensitivity induced by serotonin or histamine were both significantly inhibited by TRPV4 SiRNA intrathecal injection. Administration of sub-nociceptive doses of serotonin or histamine potentiated 4alphaPDD-induced hypersensitivity in response to CRD. CONCLUSIONS: Serotonin and histamine sensitise TRPV4 response to 4alphaPDD both in vivo (increased visceral hypersensitivity) and in vitro, in sensory neurons, by a PKC, PLA(2), PLCbeta and MAPKK-dependent mechanism. Serotonin and histamine caused a MAPKK-dependent increase in TRPV4 expression in colonic sensory neurons plasma membranes. Further, histamine- or serotonin-mediated visceral hypersensitivity depend on TRPV4 expression in sensory neurons. TRPV4 appears as a common mechanism to several known mediators of visceral hypersensitivity. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/20332520/Potentiation_of_TRPV4_signalling_by_histamine_and_serotonin:_an_important_mechanism_for_visceral_hypersensitivity_ L2 - https://gut.bmj.com/lookup/pmidlookup?view=long&pmid=20332520 DB - PRIME DP - Unbound Medicine ER -