Selective Role for TRPV4 Ion Channels in Visceral Sensory Pathways

Brierley, Stuart M.; Page, Amanda J.; Hughes, Patrick A.; Adam, Birgit; Liebregts, Tobias; Cooper, Nicole J.; Holtmann, Gerald; Liedtke, Wolfgang; Blackshaw, L. Ashley

doi:10.1053/j.gastro.2008.01.074

Cited by 231 publications

(249 citation statements)

References 29 publications

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“…121 This ion channel is gated by osmotic swelling, mechanical distortion, endogenous 5',6'epoxyeicosatrienoic acid, anandamide and 2-AG (2-arachidonoylglycerol) and, in a partially desensitizing fashion, by tem-perature >27˚C. 122 Mechanically-induced firing of vascular afferents is attenuated in TRPV4-null mice and by a TRPV4 channel blocker.…”

Section: Trp Channels In Vascular Afferentsmentioning

confidence: 99%

“…122 Mechanically-induced firing of vascular afferents is attenuated in TRPV4-null mice and by a TRPV4 channel blocker. 121 Conversely, a TRPV4 agonist causes hypersensitivity to distension and enhanced afferent responses to distension. 121,123 TRPV4 is extensively co-localised with PAR2 (proteinase-activated receptor 2), which sensitizes thoracolumbar spinal afferents to the gut during neurogenic inflammation.…”

Section: Trp Channels In Vascular Afferentsmentioning

confidence: 99%

“…121 Conversely, a TRPV4 agonist causes hypersensitivity to distension and enhanced afferent responses to distension. 121,123 TRPV4 is extensively co-localised with PAR2 (proteinase-activated receptor 2), which sensitizes thoracolumbar spinal afferents to the gut during neurogenic inflammation. 124 Activation of PAR2, by proteases released by mast cell degranulation, can lead to behavioural hypersensitivity and increased afferent firing via sensitization of TRPV4.…”

Section: Trp Channels In Vascular Afferentsmentioning

confidence: 99%

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Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

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Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors, and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that there are just five structurally distinct types of sensory endings in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators.Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.2

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Section: Trp Channels In Vascular Afferentsmentioning

confidence: 99%

Section: Trp Channels In Vascular Afferentsmentioning

confidence: 99%

Section: Trp Channels In Vascular Afferentsmentioning

confidence: 99%

See 1 more Smart Citation

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

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“…Colo-rectal single unit extracellular electrophysiological recordings from muscular / mucosal afferents from the pelvic nerve were performed as previously described (Brierley et al, 2009;Brierley et al, 2004;Brierley et al, 2008;Hughes et al, 2009b;Hughes et al, 2013a). Briefly the distal colo-rectum plus attached pelvic nerves were removed from the mice, the colo-rectum opened up longitudinally and pinned mucosal side up in a specialized organ bath.…”

Section: Electrophysiologymentioning

confidence: 99%

“…TCATTCCTCTGTCCATGCAA)) was compared between healthy and CVH mice using the comparative cycle threshold method with tubb3 (primers: forward CCAAGTTCTGGGAGGTCATC, reverse TGAGAGGAGGCCTCATTGTAG) as a housekeeper, as previously described (Brierley et al, 2009;Brierley et al, 2008;Hughes et al, 2007;Hughes et al, 2013a).…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients, Brain, Behavior, and Immunity (2014), doi: http://dx.doi.org/10. 1016/j.bbi.2014.07.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-endorphin was identified predominantly in monocyte / macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in µ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte / macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.

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TRP Channels and Human Diseases

Nilius

Vennekens

2010

Vanilloid Receptor TRPV1 in Drug Discovery

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Selective Role for TRPV4 Ion Channels in Visceral Sensory Pathways

Cited by 231 publications

References 29 publications

Extrinsic primary afferent signalling in the gut

Extrinsic primary afferent signalling in the gut

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

TRP Channels and Human Diseases

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