Purinergic mechanisms contribute to mechanosensory transduction in the rat colorectum

Wynn, Greg; Rong, Weifang; Xiang, Zhenghua; Burnstock, Geoffrey

doi:10.1016/j.gastro.2003.07.008

Cited by 98 publications

(118 citation statements)

References 58 publications

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“…They may be directly activated by mechanical forces via tethering molecules to the extracellular and/or intracellular environment, as has been described for the degenerin family of proteins, relatives of the ASICs found in Drosophila (Welsh et al, 2002). Alternatively, they may be indirectly activated by diffusible secondary messengers released from other nearby cells, analogous to the participation of purinergic receptors in visceral mechanosensation (Wynn et al, 2003). Future experiments will elucidate which of these (or other) mechanisms is responsible.…”

Section: 2001mentioning

confidence: 93%

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: 2001mentioning

confidence: 93%

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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“…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

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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“…However, subtype-specific motifs are mainly located in the C-terminus, such as motifs 27 and 35 in mammalian P2X6, which is thought to be involved in desensitization [56]. A series of P2X7-specific motifs (motifs 19,24,23,20,16, and 21) was found, which can constitute a longer TM2 domain enabling P2X7 receptors to provide a pathway that allows the passage of larger organic cations [57,58]. In addition, some primitive species (Aqu-p2xa, Sko-p2xa, Nve-p2xa) share a series of conserved motifs with advanced species, while some homologous short motifs were also detected in Fig.…”

Section: Phylogenetic Analysis Of the Putative P2x Genesmentioning

confidence: 99%

“…P2X3, P2X2, P2X4, and P2X6 receptors are reported to be involved in neurotransmission and neuromodulation [17,18]. Several P2X subtypes, such as P2X2, P2X3, P2X4, and P2X7, are involved in the reflex activities of guts in rats [19,20]. The expression of P2X1, P2X3, P2X4, P2X5, and P2X6 in the heart affects the modulation of cardiac contractility of mice [21].…”

Section: Introductionmentioning

confidence: 99%

Comparative study of the P2X gene family in animals and plants

Hou

Cao

2016

Purinergic Signalling

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P2X receptors are ligand-gated ion channels that can bind with the adenosine triphosphate (ATP) and have diverse functional roles in neuropathic pain, inflammation, special sense, and so on. In this study, 180 putative P2X genes, including 176 members in 32 animal species and 4 members in 3 species of lower plants, were identified. These genes were divided into 13 groups, including 7 groups in vertebrates and 6 groups in invertebrates and lower plants, through phylogenetic analysis. Their gene organization and motif composition are conserved in most predicted P2X members, while groupspecific features were also found. Moreover, synteny relationships of the putative P2X genes in vertebrates are conserved while simultaneously experiencing a series of gene insertion, inversion, and transposition. Recombination signals were detected in almost all of the vertebrates and invertebrates, suggesting that intragenic recombination may play a significant role in the evolution of P2X genes. Selection analysis also identified some positively selected sites that acted on the evolution of most of the predicted P2X proteins. The phenomenon of alternative splicing occurred commonly in the putative P2X genes of vertebrates. This article explored in depth the evolutional relationship among different subtypes of P2X genes in animal and plants and might serve as a solid foundation for deciphering their functions in further studies.

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Purinergic mechanisms contribute to mechanosensory transduction in the rat colorectum

Cited by 98 publications

References 58 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

Extrinsic primary afferent signalling in the gut

Comparative study of the P2X gene family in animals and plants

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