Histamine excites neurones in the human submucous plexus through activation of H1, H2, H3 and H4 receptors

Breunig, Eva; Michel, Klaus; Zeller, Florian; Seidl, Stefan; Weyhern, Claus W. Hann von; Schemann, Michael

doi:10.1113/jphysiol.2007.139352

Cited by 129 publications

(130 citation statements)

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“…H4R expression has been reported in peripheral nerves and in the neurons of the submucous plexus (Nakaya et al, 2004;Breunig et al, 2007). More recently it has been observed the presence of H4R receptors in numerous areas of the central nervous system (CNS), such as hippocampus, thalamus, amygdala, cortex, striatum and spinal cord (Strakhova et al, 2009;Connelly et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic effect of histamine H4 receptor modulation in the central nervous system

2013

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a b s t r a c tThe histamine H4 receptor (H4R) is expressed primarily on cells involved in inflammation and immune responses. Recently, it has been reported the functional expression of H4R within neurons of the central nervous system, but their role has been poorly understood. The present study aimed to elucidate the physiopathological role of cerebral H4R in animal models by the intracerebroventricular administration of the H4R agonist VUF 8430 (20e40 mg per mouse). Selectivity of results was confirmed by the prevention of the effects produced by the H4R antagonist JNJ 10191584 (3e9 mg/kg p.o.). Neuronal H4R activation induced acute thermal antinociception, indicating that neuronal histamine H4R might be involved in the production of antinociception in the absence of an inflammatory process. An anxiolyticlike effect of intensity comparable to that exerted by diazepam, used as reference drug, was produced in the lightedark box test. VUF 8430 reversed the scopolamine-induced amnesia in the passive avoidance test and showed anorexant activity in food deprived mice. Conversely, the H4R activation did not modify the immobility time in the tail suspension test. Rotarod performance test was employed to demonstrate that the effects observed following the administration of VUF 8430 and JNJ 10191584 were not due to impaired motor function of animals. Furthermore, both compounds did not alter spontaneous mobility and exploratory activity in the hole board test. These results show the antinociceptive, antiamnesic, anxiolytic and anorexant effects induced by neuronal H4R agonism, suggesting that H4 modulators may have broader utility further the control of inflammatory and immune processes.

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Section: Introductionmentioning

confidence: 99%

Pleiotropic effect of histamine H4 receptor modulation in the central nervous system

2013

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“…Whereas, presynaptic H 3 R suppress release of noradrenalin from sympathetic terminals, and thereby enhance the neurogenic secretomotor responses that underlie diarrhea. 49,50 PAR1 and PAR2 expressed on myenteric neurons have been reported to modulate gut motility in different ways, for example, promote con-traction of gastric smooth muscle but reduce contractility of both circular and longitudinal colonic smooth muscles. 51,52 But changed expression ratio of PAR1 to PAR2 in the colon is connected with D-IBS patients, 53 which may partly associated with increased motility.…”

Section: Mast Cells Regulate Gastrointestinal Motilitymentioning

confidence: 99%

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

111

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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“…EC 50 and IC50 values are extrapolated from sigmoid cumulative concentration-response curves fitted by a nonlinear curve fitting program (GraphPad Prism 3 applied to Figs. [5][6][7][8]. Statistical analysis was done by using Stat-View 54.51 (Abacus Concepts, Calabasas, CA).…”

Section: Methodsmentioning

confidence: 99%

Activation of adenosine low-affinity A3 receptors inhibits the enteric short interplexus neural circuit triggered by histamine

Bozarov

Wang

Yu³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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We tested the novel hypothesis that endogenous adenosine (eADO) activates low-affinity A3 receptors in a model of neurogenic diarrhea in the guinea pig colon. Dimaprit activation of H2 receptors was used to trigger a cyclic coordinated response of contraction and Cl Ϫ secretion. Contraction-relaxation was monitored by sonomicrometry (via intracrystal distance) simultaneously with short-circuit current (Isc, Cl Ϫ secretion). The short interplexus reflex coordinated response was attenuated or abolished by antagonists at H2 (cimetidine), 5-hydroxytryptamine 4 receptor (RS39604), neurokinin-1 receptor (GR82334), or nicotinic (mecamylamine) receptors. The A1 agonist 2-chloro- -(3-iodobenzyl)-adenosine-5Ј-N-methyluronamide (IB-MECA) abolished coordinated responses and the A3 antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(Ϯ)-dihydropyridine-3,5-dicarboxylate (MRS1191) could restore and further augment responses. The IB-MECA effect was resistant to knockdown of adenosine A1 receptor with the irreversible antagonist FSCPX; the IC50 for IB-MECA was 0.8 M. MRS1191 alone could augment or unmask coordinated responses to dimaprit, and IB-MECA suppressed them. MRS1191 augmented distension-evoked reflex Isc responses. Adenosine deaminase mimicked actions of adenosine receptor antagonists. A3 receptor immunoreactivity was differentially expressed in enteric neurons of different parts of colon. After tetrodotoxin, IB-MECA caused circular muscle relaxation. The data support the novel concept that eADO acts at low-affinity A3 receptors in addition to high-affinity A1 receptors to suppress coordinated responses triggered by immune-histamine H2 receptor activation. The short interplexus circuit activated by histamine involves adenosine, acetylcholine, substance P, and serotonin. We postulate that A3 receptor modulation may occur in gut inflammatory diseases or allergic responses involving mast cell and histamine release. adenosine A3 receptor; adenosine A1 receptor; neurogenic diarrhea; sonomicrometry; motility; Cl Ϫ secretion; coordination of motility and secretion; endogenous adenosine ADENOSINE (ADO) A1, A2, and A3 receptor (R) proteins or mRNA exist in rodent (30) and human intestinal tract (14). Functional evidence for A1 inhibitory, non-A1 (putative A3), and A2 excitatory receptors exists on enteric neurons (15). A preliminary report suggested that an inhibitory limb of the musculomotor reflex may be activated by putative A3 receptors in the rodent distal colon (24). One study to date provided pharmacological evidence for inhibitory A3 receptors in synaptic transmission in neurons of the intact submucosal plexus of the human jejunum (65). Endogenous adenosine (eADO) provides ongoing inhibitory effects in enterochromaffin (EC) cells (17) and the enteric nervous system (ENS) in rodents (13,15,16,18) and humans (65) and in hypoxic conditions (29) by activating high-affinity A1 and putative low-affinity A3 receptors. This has been deduced from pharmacological studies with selective agonists or antagonists at the...

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Histamine excites neurones in the human submucous plexus through activation of H₁, H₂, H₃ and H₄ receptors

Cited by 129 publications

References 39 publications

Pleiotropic effect of histamine H4 receptor modulation in the central nervous system

Pleiotropic effect of histamine H4 receptor modulation in the central nervous system

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Activation of adenosine low-affinity A3 receptors inhibits the enteric short interplexus neural circuit triggered by histamine

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