Number and Distribution of Intraganglionic Laminar Endings in the Mouse Esophagus as Demonstrated with Two Different Immunohistochemical Markers

Raab, M.; Neuhuber, Winfried

doi:10.1369/jhc.4a6582.2005

Cited by 25 publications

(36 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the esophagus, ATP released from esophageal keratinocytes may act in different ways on nerve endings that innervate the esophagus. ATP may reach and activate purinergic receptors expressed in intraganglionic laminar endings (23,37,45), since they are in intestine (3). Alternatively, vagal and spinal mucosal afferents may detect released ATP because they abut on and penetrate the esophageal epithelium with small branches (17,30,45).…”

Section: Resultsmentioning

confidence: 99%

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

Altomare

Rieder

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

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...

show abstract

Section: Resultsmentioning

confidence: 99%

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

Altomare

Rieder

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…L airway lumen pulmonary NEBs were applied (Brouns et al 2000(Brouns et al , 2002a(Brouns et al , b, 2003(Brouns et al , 2006aPintelon et al 2003). Because VGLUT1, VGLUT2 and P2X 2 receptor staining has been reported in putative vagal mechanosensory intraganglionic laminar endings (IGLEs) in the mouse esophagus (Castelucci et al 2003;Raab and Neuhuber 2005;Kraus et al 2007), this organ served as handy positive control in all of our en bloc lung-esophagus-heart cryostat sections. Moreover, for VGLUT1 and VGLUT2, the same antibodies as described in the latter studies were utilized (Raab and Neuhuber 2005;Kraus et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Due to the en bloc dissection and sectioning of intrathoracic organs, the esophagus was typically included as a positive control for VGLUT1 (Kraus et al 2007), VGLUT2 (Raab and Neuhuber 2003) and P2X 2 receptor immunostaining (Castelucci et al 2003;Raab and Neuhuber 2005). Negative staining controls for all immunohistochemical procedures were performed by substitution of primary or secondary antisera for non-immune sera.…”

Section: Control Experiments For the Immunohistochemical Proceduresmentioning

confidence: 99%

“…In rodents, the vagal sensory innervation of pulmonary NEBs expresses VGLUTs, calcium-binding proteins and P2X 2/3 receptors, proteins that have been reported as markers for IGLE mechanoreceptor terminals in the esophagus (Raab and Neuhuber 2003;Castelucci et al 2003;Raab and Neuhuber 2005;Kraus et al 2007). It may, therefore, be proposed that vagal sensory terminals in rodent NEBs should be regarded as the morphological counterparts of at least certain subpopulations of electrophysiologically identiWed vagal mechanoreceptors (Adriaensen et al 2006;Brouns et al 2006a, b;Timmermans and Adriaensen 2008).…”

Section: Fig 26mentioning

confidence: 99%

See 1 more Smart Citation

Neurochemical pattern of the complex innervation of neuroepithelial bodies in mouse lungs

Brouns

Öztay

Pintelon

et al. 2008

Histochem Cell Biol

View full text Add to dashboard Cite

As best characterized for rats, it is clear that pulmonary neuroepithelial bodies (NEBs) are contacted by a plethora of nerve fiber populations, suggesting that they represent an extensive group of multifunctional intraepithelial airway receptors. Because of the importance of genetically modified mice for functional studies, and the current lack of data, the main aim of the present study was to achieve a detailed analysis of the origin and neurochemical properties of nerve terminals associated with NEBs in mouse lungs. Antibodies against known selective markers for sensory and motor nerve terminals in rat lungs were used on lungs from control and vagotomized mice of two different strains, i.e., Swiss and C57-Bl6. NEB cells were visualized by antibodies against either the general neuroendocrine marker protein gene-product 9.5 (PGP9.5) or calcitonin gene-related peptide (CGRP). Thorough immunohistochemical examination of NEB cells showed that some of these NEB cells also exhibit calbindin D-28 k (CB) and vesicular acetylcholine transporter (VAChT) immunoreactivity (IR). Mouse pulmonary NEBs were found to receive intraepithelial nerve terminals of at least two different populations of myelinated vagal afferents: (1) Immunoreactive (ir) for vesicular glutamate transporters (VGLUTs) and CB; (2) expressing P2X(2) and P2X(3) ATP receptors. CGRP IR was seen in varicose vagal nerve fibers and in delicate non-vagal fibers, both in close proximity to NEBs. VAChT immunostaining showed very weak IR in the NEB-related intraepithelial vagal sensory nerve terminals. nNOS- or VIP-ir nerve terminals could be observed at the base of pulmonary NEBs. While a single NEB can be contacted by multiple nerve fiber populations, it was clear that none of the so far characterized nerve fiber populations contacts all pulmonary NEBs. The present study revealed that mouse lungs harbor several populations of nerve terminals that may selectively contact NEBs. Although at present the physiological significance of the innervation pattern of NEBs remains enigmatic, it is likely that NEBs are receptor-effector end-organs that may host complex and/or multiple functional properties in normal airways. The neurochemical information on the innervation of NEBs in mouse lungs gathered in the present study will be essential for the interpretation of upcoming functional data and for the study of transgenic mice.

show abstract

“…Myenteric mechanoreceptors showed none of characteristics of the leaf-like lamellar endings associated with IGLEs in the upper GI-tract, or rIGLEs in the lower GItract. Myenteric mechanoreceptors were readily identified by their immunoreactivity to the TRPV1 antibody and their immunoreactivity to the glutamate transporter, Vglut2, a reliable marker for extrinsic afferents in the GI-tract (Raab and Neuhuber, 2005;Zagorodnyuk and Brookes, 2003). These TRPV1 bulbous nodules were first identified morphologically in the distal colon of guinea pigs and mice in the immunohistochemical study by Ward et al (2003) but, at that stage, it was not shown that they behaved physiologically as a capsaicinsensitive low threshold mechanoreceptor.…”

mentioning

confidence: 99%

Identification of capsaicin-sensitive rectal mechanoreceptors activated by rectal distension in mice

et al. 2008

View full text Add to dashboard Cite

Rodents detect visceral pain in response to noxious levels of rectal distension. However, the mechanoreceptors that innervate the rectum and respond to noxious levels of rectal distension have not been identified. Here, we have identified the mechanoreceptors of capsaicin-sensitive rectal afferents and characterized their properties in response to circumferential stretch of the rectal wall. We have also used the lethal spotted (ls/ls) mouse to determine whether rectal mechanoreceptors that respond to capsaicin and stretch may also develop in an aganglionic rectum that is congenitally devoid of enteric ganglia. In wild type (C57BL/6) mice, graded increases in circumferential stretch applied to isolated rectal segments activated a graded increase in firing of slowly-adapting rectal mechanoreceptors. Identical stimuli applied to the aganglionic rectum of ls/ls mice also activated similar graded increases in firing of stretch-sensitive rectal afferents. In both wild type and aganglionic rectal preparations, focal compression of the serosal surface using von Frey hairs identified mechanosensitive "hot spots," that were associated with brief bursts of action potentials. Spritzing capsaicin (10 microM) selectively onto each identified mechanosensitive hot spot activated an all or none discharge of action potentials in 32 of 56 identified hot spots in wild type mice and 24 of 62 mechanosensitive hot spots in the aganglionic rectum of ls/ls mice. Each single unit activated by both capsaicin and circumferential stretch responded to low mechanical thresholds (1-2 g stretch). No high threshold rectal afferents were ever recorded in response to circumferential stretch. Anterograde labeling from recorded rectal afferents revealed two populations of capsaicin-sensitive mechanoreceptor that responded to stretch: one population terminated within myenteric ganglia, the other within the circular and longitudinal smooth muscle layers. In the aganglionic rectum of ls/ls mice, only the i.m. mechanoreceptors were identified. Both myenteric and i.m. mechanoreceptors could be identified by their immunoreactivity to the anti-TRPV1 antibody and the vesicular glutamate transporter, Vglut2. Myenteric mechanoreceptors had a unique morphology, consisting of smooth bulbous nodules that ramified within myenteric ganglia. In summary, the rectum of wild type mice is innervated by at least two populations of capsaicin-sensitive rectal mechanoreceptor, both of which respond to low mechanical thresholds within the innocuous range. These findings suggest that the visceral pain pathway activated by rectal distension is likely to involve low threshold rectal mechanoreceptors that are activated within the normal physiological range.

show abstract

Number and Distribution of Intraganglionic Laminar Endings in the Mouse Esophagus as Demonstrated with Two Different Immunohistochemical Markers

Cited by 25 publications

References 34 publications

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

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

Neurochemical pattern of the complex innervation of neuroepithelial bodies in mouse lungs

Identification of capsaicin-sensitive rectal mechanoreceptors activated by rectal distension in mice

Contact Info

Product

Resources

About