CO2 chemosensing in rat oesophagus

Akiba, Yasutada; Mizumori, Misa; Kuo, Myrna; Ham, Maggie; Guth, Paul H.; Engel, Eli; Kaunitz, Jonathan D.

doi:10.1136/gut.2007.144378

Cited by 54 publications

(50 citation statements)

References 46 publications

(84 reference statements)

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“…The HET-1A cell line retains epithelial morphology, stains positively for cytokeratins, and is nontumorigenic (40). We previously demonstrated (27) that HET-1A cells contain TRPV1 receptors that are linked to increased cytosolic Ca 2ϩ and produce PAF in response to the selective TRPV1 agonist capsaicin, confirming that TRPV1 receptors are present not only in submucosal neurons, as previously demonstrated (4,29), but also in the epithelial cells themselves (14), in agreement with recent data by Akiba et al (1).…”

Section: Resultssupporting

confidence: 92%

ATP: a mediator for HCl-induced TRPV1 activation in esophageal mucosa

Altomare

Rieder

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Harnett KM. ATP: a mediator for HCl-induced TRPV1 activation in esophageal mucosa. Am J Physiol Gastrointest Liver Physiol 301: G1075-G1082, 2011. First published September 29, 2011 doi:10.1152/ajpgi.00336.2011In esophageal mucosa, HCl causes TRPV1-mediated release of calcitonin gene-related peptide (CGRP) and substance P (SP) from submucosal neurons and of platelet-activating factor (PAF) from epithelial cells. CGRP and SP release was unaffected by PAF antagonists but reduced by the purinergic antagonist suramin. ATP caused CGRP and SP release from esophageal mucosa, confirming a role of ATP in the release. The human esophageal epithelial cell line HET-1A was used to identify epithelial cells as the site of ATP release. HCl caused ATP release from HET-1A, which was reduced by the TRPV1 antagonist 5-iodoresiniferatoxin. Real-time PCR demonstrated the presence of mRNA for several P2X and P2Y purinergic receptors in epithelial cells. HCl also increased activity of lyso-PAF acetyl-CoA transferase (lyso-PAF AT), the enzyme responsible for production of PAF. The increase was blocked by suramin. ATP caused a similar increase, confirming ATP as a mediator for the TRPV1-induced increase in enzyme activity. Repeated exposure of HET-1A cells to HCl over 2 days caused upregulation of mRNA and protein expression for lyso-PAF AT. Suramin blocked this response. Repeated exposure to ATP caused a similar mRNA increase, confirming ATP as a mediator for upregulation of the enzyme. Thus, HCl-induced activation of TRPV1 causes ATP release from esophageal epithelial cells that causes release of CGRP and SP from esophageal submucosal neurons and activation of lyso-PAF AT, the enzyme responsible for the production of PAF in epithelial cells. Repeated application of HCl or of ATP causes upregulation of lyso-PAF AT in epithelial cells. purinergic receptors; vanilloid receptors; platelet-activating factor; calcitonin gene-related peptide; substance P ESOPHAGITIS WAS THOUGHT TO develop from a chemical injury starting at the luminal surface of the squamous epithelium, progressing through epithelium and lamina propria into the submucosa and resulting in acid-induced death of surface cells and stimulation of a proliferative response in the basal cells (20). Epithelial cells were viewed as bystanders in the process of inflammation, functioning primarily as a protective barrier to infiltration of noxious chemicals and bacteria into the underlying tissue. Recent evidence, however, in the urinary bladder (5) and in the esophagus suggests that these cells function as primary transducers of physical and chemical stimuli and communicate with underlying cells, including nerves (14), smooth muscle (11,12), and even inflammatory cells (26).We propose that acid-induced inflammation of the esophagus begins with activation of acid-sensitive vanilloid receptors (TRPV1) in the mucosa. TRPV1 activation induces synthesis and release of the sensory neurotransmitters calcitonin generelated peptide (CGRP) and substance P (SP) from submucosal neurons and of the...

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Section: Resultssupporting

confidence: 92%

ATP: a mediator for HCl-induced TRPV1 activation in esophageal mucosa

Altomare

Rieder

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The HET-1A cell line has been shown to retain epithelial morphology, stains positively for cytokeratins, and has remained nontumorigenic (49). We demonstrate here that HET-1A cells contain vanilloid receptors that are linked to increased cytosolic calcium and produce PAF in response to the selective TRPV1 agonist capsaicin, confirming that TRPV1 receptors are present not only in submucosal neurons, as previously demonstrated (8,29), but also in the epithelial cells themselves (17), in agreement with recent data by Akiba et al (1).…”

Section: Discussionsupporting

confidence: 92%

Signaling in TRPV1-induced platelet activating factor (PAF) in human esophageal epithelial cells

Harnett

Behar

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Transient receptor potential channel, vanilloid subfamily member 1 (TRPV1) receptors were identified in human esophageal squamous epithelial cell line HET-1A by RT-PCR and by Western blot. In fura-2 AM-loaded cells, the TRPV1 agonist capsaicin caused a fourfold cytosolic calcium increase, supporting a role of TRPV1 as a capsaicin-activated cation channel. Capsaicin increased production of platelet activating factor (PAF), an important inflammatory mediator that acts as a chemoattractant and activator of immune cells. The increase was reduced by the p38 MAP kinase (p38) inhibitor SB203580, by the cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF3, and by the lyso-PAF acetyltransferase inhibitor sanguinarin, indicating that capsaicin-induced PAF production may be mediated by activation of cPLA(2), p38, and lyso-PAF acetyltransferase. To establish a sequential signaling pathway, we examined the phosphorylation of p38 and cPLA(2) by Western blot. Capsaicin induced phosphorylation of p38 and cPLA(2). Capsaicin-induced p38 phosphorylation was not affected by AACOCF3. Conversely, capsaicin-induced cPLA(2) phosphorylation was blocked by SB203580, indicating that capsaicin-induced PAF production depends on sequential activation of p38 and cPLA(2). To investigate how p38 phosphorylation may result from TRPV1-mediated calcium influx, we examined a possible role of calmodulin kinase (CaM-K). p38 phosphorylation was stimulated by the calcium ionophore A23187 and by capsaicin, and the response to both agonists was reduced by a CaM inhibitor and by CaM-KII inhibitors, indicating that calcium induced activation of CaM and CaM-KII results in P38 phosphorylation. Acetyl-CoA transferase activity increased in response to capsaicin and was inhibited by SB203580, indicating that p38 phosphorylation in turn causes activation of acetyl-CoA transferase to produce PAF. Thus epithelial cells produce PAF in response to TRPV1-mediated calcium elevation.

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“…Similar to the duodenal acid sensing, the esophageal mucosa also senses luminal acidity as the permeant gas CO 2 with help of epithelial and neuronal CA activities and acid sensors, TRPV1 and acid-sensing ion channels (ASICs), in order to maintain the interstitial pH at a physiological level via the hyperemic response to luminal H + /CO 2 [1,24]. The concept that CA activity and acid sensors are the essential components of H + /CO 2 sensing is supported by the observation that taste of carbonation on the tongue is mediated and sensed by CA activity and an acid sensor [25].…”

Section: Esophageal and Gastric Acid Sensingmentioning

confidence: 99%

Duodenal Chemosensing and Mucosal Defenses

Akiba

Kaunitz²

2011

Digestion

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The duodenal mucosa is exposed to endogenous and exogenous chemicals, including acid, CO₂, bile acids and nutrients. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption, and motility. We propose a mucosal chemosensing system by which luminal chemicals are sensed via mucosal acid sensors and G-protein-coupled receptors. Luminal acid/CO₂ sensing consists of ecto- and cytosolic carbonic anhydrases, epithelial ion transporters, and acid sensors expressed on the afferent nerves in the duodenum. Furthermore, a luminal L-glutamate signal is mediated via mucosal L-glutamate receptors, including metabotropic glutamate receptors and taste receptor 1 family heterodimers, with activation of afferent nerves and cyclooxygenase, whereas luminal Ca²⁺ is differently sensed via the calcium-sensing receptor in the duodenum. Recent studies also show the involvement of enteroendocrine G-protein-coupled receptors in bile acid and fatty acid sensing in the duodenum. These luminal chemosensors help activate mucosal defense mechanisms in or- der to maintain the mucosal integrity and physiological responses. Stimulation of luminal chemosensing in the duodenal mucosa may prevent mucosal injury, affect nutrient metabolism, and modulate sensory nerve activity.

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CO2 chemosensing in rat oesophagus

Cited by 54 publications

References 46 publications

ATP: a mediator for HCl-induced TRPV1 activation in esophageal mucosa

ATP: a mediator for HCl-induced TRPV1 activation in esophageal mucosa

Signaling in TRPV1-induced platelet activating factor (PAF) in human esophageal epithelial cells

Duodenal Chemosensing and Mucosal Defenses

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