Mechanotransduction by intraganglionic laminar endings of vagal tension receptors in the guinea‐pig oesophagus

Zagorodnyuk, Vladimir; Chen, Bao Nan; Costa, Marcello; Brookes, Simon Jonathan

doi:10.1113/jphysiol.2003.051862

Cited by 133 publications

(162 citation statements)

References 66 publications

(83 reference statements)

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“…Although mechanosensitive structures have not been described in the small or large intestine, circumferential stretch of the esophagus, stomach, and rectum is thought to be detected by intraganglionic laminar endings (IGLEs) (Lynn et al, 2003;Zagorodnyuk and Brooks, 2000;Zagorodnyuk et al, 2001). Indeed, Zagorodnyuk et al (2003) recently reported that esophageal IGLEs directly transduce mechanical stimuli. The identity of the molecules that confer mechanosensitivity to these structures is unknown, but we provide evidence to suggest that TRPV1 and ASIC3 may contribute to this function.…”

Section: Discussionmentioning

confidence: 99%

The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

Jones¹,

Xu²,

Gebhart³

2005

J. Neurosci.

383

308

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Mechanical hypersensitivity of the colon underlies in part the chronic abdominal pain experienced by patients with irritable bowel syndrome, yet the molecules that confer mechanosensitivity to colon sensory neurons and their contribution to visceral pain are unknown. We tested the hypothesis that transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel 3 (ASIC3) are peripheral mechanosensors in colon afferent neuronal fibers that mediate visceral nociceptive behavior in mice. Visceral nociception, modeled by the visceromotor response to colorectal distension, and colon afferent fiber mechanosensitivity were assessed in control (C57BL/6) mice and two congenic knock-out mouse strains with deletions of either TRPV1 or ASIC3. Phasic colon distension (15-60 mmHg) produced graded behavioral responses in all three mouse strains. However, both TRPV1 and ASIC3 knock-out mice were significantly less sensitive to distension, with an average response magnitude only 58 and 50% of controls, respectively. The behavioral deficits observed in both strains of knock-out mice were associated with a significant and selective reduction in afferent fiber sensitivity to circumferential stretch of the colon, an effect that was mimicked in control preparations by pretreatment with capsazepine, a TRPV1 antagonist, but not amiloride, a nonselective ASIC antagonist (both 500 M). In addition, whereas stretch-evoked afferent fiber responses were enhanced by chemical inflammatory mediators in control mice, this effect was differentially impaired in both knock-out mouse strains. These results demonstrate a peripheral mechanosensory role for TRPV1 and ASIC3 in the mouse colon that contributes to nociceptive behavior and possibly peripheral sensitization during tissue insult.

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Section: Discussionmentioning

confidence: 99%

The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

Jones¹,

Xu²,

Gebhart³

2005

J. Neurosci.

383

308

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“…IGLEs are the mechanotransduction sites of vagal tension receptors (Zagorodnyuk and Brookes, 2000;Zagorodnyuk et al, 2003), the nNOS inhibitor did not affect their mechanosensitivity. Therefore, the NO produced by myenteric neurons does not reach IGLEs surrounding them at sufficient concentrations.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide as an Endogenous Peripheral Modulator of Visceral Sensory Neuronal Function

Page¹,

O’Donnell²,

Cooper³

et al. 2009

J. Neurosci.

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“…By comparing dye-filled nerve endings with carbon marks on the tissue, the sensory endings of low-threshold vagal mechanoreceptors were shown to correspond to intraganglionic laminar endings (IGLEs) located in myenteric ganglia. 24,25 These IGLEs detect distortion of the surrounding tissue by as-yet-unidentified stretchactivated ion channels 26 and probably signal gastric distension after a meal. They end inparallel with the smooth muscle fibres of the gut wall, yet respond mechanically as in-series tension receptors.…”

Section: Vagal Intraganglionic Laminar Mechanoreceptorsmentioning

confidence: 99%

“…32 An intriguing feature of IGLEs, shared by many other visceral afferents, is their sensitivity to a range of biological mediators. IGLEs are potently excited by ATP, 26,33 probably when this biochemical is released from damaged cells 34 ATP might also couple mechanosensitive epi-thelia to excitation of mechanoreceptors; 35,36 however, the time course of ATP release and its effects preclude a role in mechanotransduction by IGLEs. 26 The same endings in ferret stomach and oesophagus express inhibitory GABA B receptors, 37 excitatory and inhibitory metabotropic glutamate receptors 38,39 and are inhibited by ghrelin.…”

Section: Vagal Intraganglionic Laminar Mechanoreceptorsmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

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240

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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Mechanotransduction by intraganglionic laminar endings of vagal tension receptors in the guinea‐pig oesophagus

Cited by 133 publications

References 66 publications

The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

Nitric Oxide as an Endogenous Peripheral Modulator of Visceral Sensory Neuronal Function

Extrinsic primary afferent signalling in the gut

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