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Biomedical subjects

M Schemann

Publications and source records attributed to M Schemann.

At least 19 recordsLinked to original sources
PubMed2006

Region-specific effects of STW 5 (Iberogast) and its components in gastric fundus, corpus and antrum.

Functional dyspepsia (FD) is a disorder that involves impaired gastric accommodation, antral hypomotility, and upper abdominal pain. The herbal drug STW 5 (Iberogast) is used to successfully treat FD patients. Here, we report in vitro data revealing the mode of action of STW 5 and its individual herbal extracts on gastric motility. STW 5 evoked a relaxation of the proximal stomach but increased antral motility. Both effects are myogenic. The extracts of Angelica root, chamomile flower and liquorice root mimicked the inhibitory effects in the proximal stomach whereas the extracts of greater celandine herb, Melissa leaf, caraway fruit and bitter candy tuft increased motility of the proximal stomach. All extracts increased motility in the antrum comparable to the effects of STW 5. We conclude that the differential effects of STW 5 on proximal and distal stomach motor activity are not caused by solely spasmolytic or anti-spasmolytic effects of the individual components. It is suggested that the individual extracts target transduction mechanisms that are specifically expressed in the proximal vs. distal stomach. We present a rationale for the differential effect of STW 5 which is a result of the combined actions of its individual components and reason that the inhibitory effects in the proximal and the excitatory effects in the distal stomach may contribute to symptom relief in FD patients treated with STW 5 (Iberogast).

Animals↗
PubMed2005

Human mast cell mediator cocktail excites neurons in human and guinea-pig enteric nervous system.

Neuroimmune interactions are an integral part of gut physiology and involved in the pathogenesis of inflammatory and functional bowel disorders. Mast cells and their mediators are important conveyors in the communication from the innate enteric immune system to the enteric nervous system (ENS). However, it is not known whether a mediator cocktail released from activated human mast cells affects neural activity in the ENS. We used the Multi-Site Optical Recording Technique to image single cell activity in guinea-pig and human ENS after application of a mast cell mediator cocktail (MCMC) that was released from isolated human intestinal mucosa mast cells stimulated by IgE-receptor cross-linking. Local application of MCMC onto individual ganglia evoked an excitatory response consisting of action potential discharge. This excitatory response occurred in 31%, 38% or 11% neurons of guinea-pig submucous plexus, human submucous plexus, or guinea-pig myenteric plexus, respectively. Compound action potentials from nerve fibres or fast excitatory synaptic inputs were not affected by MCMC. This study demonstrates immunoneural signalling in the human gut and revealed for the first time that an MCMC released from stimulated human intestinal mast cells induces excitatory actions in the human and guinea-pig ENS.

Animals↗
PubMed2004

Effects of the probiotic yeast Saccharomyces boulardii on the neurochemistry of myenteric neurones in pig jejunum.

We studied the effects of food supplementation with Saccharomyces boulardii (S. boulardii; synonym S. cerevisiae HANSEN CBS 5926; 1 g per day for 9 days) on the presence and co-localization patterns of neuronal markers in myenteric neurones of the pig jejunum. The pan neuronal marker Hu revealed no change in the number of neuronal cell bodies per ganglion (37 +/- 7 in control vs 34 +/- 9 in the S. boulardii group). Ranked by size the following cell populations were identified: choline acetyltransferase (ChAT), calbindin-28k (CALB), substance P (SP), neurofilament 160 kD (NF-160), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), calcitonin gene-related peptide (CGRP), calretinin (CALRET). We found a significant decrease in the number of CALB myenteric neurones in animals which received S. boulardii supplemented diet. None of the other neuronal markers revealed any difference between controls and S. boulardii treated animals. The study reports transmitter-localization patterns in the myenteric plexus of the pig jejunum and provides evidence that changes in the neurochemistry of enteric neurones occur with S. boulardii supplemented diet. Although only CALB expression was altered and the functional significance of this finding remains unknown, our study identified a possible new effector level of probiotics in the gut.

Animals↗
PubMed2004

Substance P and other neuropeptides do not induce mediator release in isolated human intestinal mast cells.

Neuropeptides such as substance P (SP) and related peptides are supposed to act as mast cell agonists, and thus as mediators of neuroimmune interactions. The data supporting this hypothesis were obtained mostly from rodent experiments. Here, we studied for the first time the effect of SP and other peptides on mediator release in human intestinal mast cells, either unpurified or enriched to 85-99% purity. We found that SP at 0.1-100 micromol L(-1), or other peptides including neurokinin A and B, calcitonin gene-related peptide, vasoactive intestinal peptide and serotonin at 1 micromol L(-1) do not induce release of mediators such as histamine, sulphidoleukotrienes, and tumour necrosis factor alpha. The peptides also failed to cause mediator release in mast cells isolated from inflamed tissue derived from Crohn's disease. Using reverse transcriptase-polymerase chain reaction, flow cytometry and immunohistochemistry, we could show that human intestinal mast cells do not express the tachykinin receptors NK-1, NK-2, or NK-3 under basal conditions. However, upon stimulation by immunoglobulin E (IgE) receptor-crosslinking, which induces an extensive mediator release reaction, a subpopulation of mast cells clearly expressed NK-1, the SP receptor. In conclusion, our data show that SP and other neuropeptides do not act as secretagogues in human intestinal mast cells that have not been pre-activated by IgE receptor-crosslinking.

Cells, Cultured↗
PubMed2004

The herbal preparation STW5 (lberogast) has potent and region-specific effects on gastric motility.

Functional dyspepsia (FD) is amongst the most common functional gastrointestinal disorders. Symptomatic treatment includes the use of herbal preparations whose effects on gastric motility are unclear. The present study aimed at investigating the effects of STW 5 (Iberogast), a fixed combination of hydroethanolic herbal extracts, on gastric motility in vitro. Muscle strips from guinea-pig gastric fundus, corpus and antrum were set up in organ baths either in circular or longitudinal orientation. Addition of ethanol-free STW 5 to the organ baths (32-512 microg mL(-1)) dose-dependently evoked a sustained and reversible relaxation of circular and longitudinal fundus and corpus muscle strips without changes in phasic activity. In contrast, antral muscle strips responded to STW 5 with a significant increase in the contractile force of phasic contractions without changes in tone. All effects were resistant to tetrodotoxin (0.5 micromol L(-1)), atropine (1 micromol L(-1)), omega-conotoxin GVIA (0.5 micromol L(-1)), capsaicin (1 micromol L(-1)) or L-NAME (100 micromol L(-1)), suggesting that neither nerves nor nitric oxide pathways were involved. These data demonstrate that STW 5 profoundly alters gastric motility in a region-specific but not layer-specific manner and thus implicates Iberogast in the treatment of FD patients suffering from motility disorders with impaired fundus accommodation and/or antral hypomotility.

Animals↗
PubMed2004

The human enteric nervous system.

Decades of work in animal models have demonstrated that the enteric nervous system (ENS) plays a key role in controlling gut functions. Recent advances made it possible to extend such studies to the ENS of man in health and even in disease. Such studies have already provided new insights into the pathophysiology of inflammatory and possibly functional bowel diseases. Studies on human ENS revealed both important similarities and differences between the ENS of man and of experimental animals. Here we summarize the current state of knowledge of the electrophysiology and neurochemistry of the human ENS, including relevant reflex mediated functions in the human gut. Additionally, we review disease associated changes in human ENS properties. Finally, we highlight some research areas that hold special promise in advancing our understanding of the human ENS.

Animals↗
PubMed2003

Toxin B of Clostridium difficile activates human VIP submucosal neurons, in part via an IL-1beta-dependent pathway.

This study investigated whether toxin B of Clostridium difficile can activate human submucosal neurons and the involved pathways. Isolated segments of human colon were placed in organ culture for 3 h in the presence of toxin B or IL-1beta. Whole mounts of internal submucosal plexus were stained with antibodies against c-Fos, neuron-specific enolase (NSE), vasoactive intestinal polypeptide (VIP), and substance P (SP). The membrane potential (Vm) response of submucosal neurons to local application of toxin B and IL-1beta was determined by a multisite optical recording technique. Toxin B (0.1 to 10 ng/ml) increased the proportion of c-Fos-positive neurons dose dependently compared with the control. In the presence of toxin B (10 ng/ml), most c-Fos-positive neurons were immunoreactive for VIP (79.8 +/- 22.5%) but only 19.4 +/- 14.0% for SP. Toxin B induced a rapid rise in IL-1beta mRNA level and a sixfold increase in IL-1beta protein in supernatant after 3 h of incubation. c-Fos expression induced by toxin B was reduced dose dependently by IL-1 receptor antagonist (0.1-10 ng/ml). IL-1beta significantly increased c-Fos expression in submucosal neurons compared with the control (34.2 +/- 10.1 vs. 5.1 +/- 1.3% of NSE neurons). Microejection of toxin B had no effect on the Vm of enteric neurons. Evidence of a direct excitatory effect of IL-1beta on Vm was detected in a minority of enteric neurons. Therefore, toxin B of C. difficile activates VIP-positive submucosal neurons, at least in part, via an indirect IL-1beta-dependent pathway.

Aged↗
PubMed2003

Capsaicin-sensitive extrinsic afferents are involved in acid-induced activation of distinct myenteric neurons in the rat stomach.

Challenge of the rat gastric mucosa with 0.5 mol L(-1) HCl activates nitrergic neurons in the myenteric plexus as visualized by c-Fos immunohistochemistry. In the present study, we characterized the activated neurons more extensively by their chemical coding and investigated whether a neural pathway that involves capsaicin-sensitive extrinsic afferents and/or cholinergic neurons transmitting via nicotinic receptors contributes to the activation of myenteric neurons. In multiple labelling experiments, c-Fos was examined for co-localization with nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), enkephalin (ENK), gastrin-releasing peptide (GRP), substance P (SP), calbindin D-28k (CALB) and neurofilament 145 (NF 145). All c-Fos-positive neurons were immunoreactive for NOS, VIP, NPY and NF 145, but not for SP, ENK, GRP and CALB. Nerve fibres co-expressing NOS, VIP and NPY were predominantly found in the external muscle layer and in the muscularis mucosae but rarely in the mucosa. Pre-treatment with capsaicin or hexamethonium or a combination of both pre-treatments reduced HCl-induced c-Fos expression by 54, 66 and 63%, respectively. Acid challenge of the stomach, therefore, leads to activation of presumably inhibitory motor neurons responsible for muscle relaxation. Activation of these neurons is partly mediated by capsaicin-sensitive afferents and involves ganglionic transmission via nicotinic receptors.

Animals↗
PubMed2003

Changes in chemical coding of myenteric neurones in ulcerative colitis.

BACKGROUND: Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel diseases but it is still uncertain whether neurochemical coding of myenteric neurones is altered in ulcerative colitis (UC). AIMS: In this study we investigated transmitter co-localisation in myenteric neurones of normal colon and the colon of patients with UC. METHODS: Choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal peptide (VIP), and substance P (SP) were detected by immunohistochemical methods in whole mounts of colonic myenteric plexus of UC patients (n=10) and controls (n=8). RESULTS: The proportion of ChAT positive and VIP positive neurones relative to the NSE population did not differ in inflamed (33.3% and 9.3%, respectively) and non-inflamed segments (33.6% and 9.7%) of UC colon compared with controls (35.0% and 6.9%). The proportion of SP positive neurones was significantly larger in both inflamed (15.5%) and non-inflamed (20.3%) segments than in controls (5.9%). Analysis of changes in subpopulations showed that 26.9% of neurones were only ChAT positive in controls but that the proportion was significantly smaller in inflamed (18.8%) and non-inflamed (15.8%) areas of UC. The proportions of neurones containing ChAT and SP were significantly higher in inflamed (11.8%) and non-inflamed (13.9%) areas than in controls (5.0%). CONCLUSION: Remodelling of myenteric neurones in UC involves a shift from mainly cholinergic to more SP positive innervation. This effect may constitute part of the neuronal basis for the motility disturbances observed in UC.

Adult↗
PubMed2001

Glycine activates myenteric neurones in adult guinea-pigs.

1. We studied the effects of glycine on myenteric neurones and muscle activity in the colon and stomach of adult guinea-pigs. 2. Intracellular recordings revealed that myenteric neurones responded to local microejection of glycine (1 mM) with a fast, transient membrane potential depolarisation (57 % of 191 colonic neurones and 26 % of 50 gastric neurones). Most glycine-sensitive neurones had ascending projections and were choline acetyltransferase immunoreactive. Glycine preferentially activated neurones with a late afterhyperpolarisation (AH-neurones) and tonic spiking neurones with fast synaptic inputs (tonic S-neurones) but less frequently phasic S-neurones and inexcitable (non-spiking) neurones. The depolarisation had a reversal potential at -19 +/- 13 mV, which was increased by 18 +/- 10 % upon lowering extracellular chloride concentration and decreased by 38 +/- 14 % in furosemide (frusemide, 2 mM). 3. Strychnine (300 nM) reversibly abolished the glycine-induced depolarisation and the Cl(-) channel blocker picrotoxin (100 microM) reduced the amplitude of the depolarisation by 55 +/- 5 %. The glycine effect was a postsynaptic response because it was not changed after nerve blockade with tetrodotoxin (1 microM) or blockade of synaptic transmission in reduced extracellular [Ca(2+)]. The effect was specific since the response was not changed by the nicotinic antagonists hexamethonium (200 microM) and mecamylamine (100 microM), the GABA(A) receptor antagonist bicuculline (10 microM), the NMDA antagonist MK-801 (20 microM) or the 5-HT(3) antagonist ICS 205930 (1 microM). 4. Glycine (1 mM) induced a tetrodotoxin- and strychnine-sensitive contractile response in the colon; the contractile response in the stomach was tetrodotoxin insensitive. 5. Glycine activated myenteric neurones in the adult enteric nervous system through strychnine-sensitive mechanisms. The glycine-evoked depolarisation was caused by Cl(-) efflux and the maintenance of relatively high intracellular chloride concentrations involved furosemide-sensitive cation-chloride co-transporters.

Animals↗
PubMed2001

Neural components of distension-evoked secretory responses in the guinea-pig distal colon.

1. Using a Ussing chamber and neuronal retrograde tracing with 1,1'-didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) we characterized the afferent and efferent neuronal pathways which mediated distension-evoked secretion in the guinea-pig distal colon. 2. Acute capsaicin application (10 microM) to the serosal site of the Ussing chamber evoked a secretory response which was blocked by tetrodotoxin (1 microM), the combined application of the NK1 and NK3 receptor antagonists CP-99,994-1 and SR 142801 (1 microM), and by combined application of atropine (10 microM) and the VIP receptor antagonist VIP(6-28) (10 microM). Functional desensitization of extrinsic primary afferents by long-term application of capsaicin significantly diminished distension-evoked secretion by 46 %. 3. After functional desensitization by capsaicin, serosal application of gadolinium (100 microM) inhibited the distension-evoked chloride secretion by 54 %; the L-type Ca(2+) channel blocker nifedipine (1 microM) and the 5-HT(1P) receptor antagonist renzapride (1 microM) had no effect. The combination of atropine and VIP(6-28) or the combination of NK1 and NK3 receptor antagonists almost abolished distension-evoked secretion. 4. The secretory response evoked by electrical field stimulation, carbachol (1 microM) or VIP (1 microM) was not attenuated by gadolinium. Field stimulation-evoked chloride secretion was not affected by blockade of NK1 and NK3 receptors. 5. Twelve per cent of DiI-labelled submucosal neurones with projections to the mucosa were immunoreactive for choline acetyltransferase, substance P and calbindin and very probably represented intrinsic primary afferent neurones. 6. Distension-evoked chloride secretion was mediated by capsaicin-sensitive extrinsic primary afferents and by stretch-sensitive intrinsic primary afferent neurones. Both the extrinsic and intrinsic afferents converge on common efferent pathways. These pathways consist of VIPergic and cholinergic secretomotor neurones that are activated via NK1 and NK3 receptors.

Afferent Pathways↗
PubMed2001

Enteric pathways in the stomach.

This report summarises the characteristics of target specific projection and neurochemical coding patterns of motor and interneuronal pathways in the gastric enteric nervous system (ENS) which are involved in the innervation of the mucosa, the circular and the longitudinal muscle. The pathways were identified by retrograde tracing and further characterised by optical and intracellular recordings of the synaptic activation of muscle motor neurones, and by recordings of pathway-specific muscle responses. All motor pathways had polarised projections consisting of ascending cholinergic and descending nitrergic populations. Thus, both muscle layers were innervated by excitatory and inhibitory motor neurones. Their projections indicated the presence of intrinsic circuits that mediate excitatory and inhibitory components of a peristaltic reflex and/or are involved in reflex mediated changes in gastric tone. Although polarised projections were also identified for interneuronal pathways, a substantial proportion of descending interneurones was cholinergic. Interneurones and longitudinal muscle motor pathways had longitudinal projection preferences whereas circular muscle motor pathways had circumferential projection preferences. Target-specific coding was primarily revealed for cholinergic populations; ChAT/ENK/+/-SP neurones projected to the muscle layers, ChAT/NPY/+/-VIP projected to the mucosa and ChAT/+/-SP/+/-5-HT/+/-Calret/+/-Calb were interneurones. Muscle strip recordings revealed the functional significance of ascending excitatory and descending inhibitory pathways to the circular muscle and the prominent influence of ascending and descending cholinergic interneurones which activated excitatory and inhibitory circular muscle motor neurones through nicotinic synapses. It is concluded that enteric pathways in the stomach have region specific features which reflect structural and functional adaptation of the gastric ENS.

Animals↗
PubMed2001

Neurochemically distinct myenteric neurone populations containing calbindin have specific distribution patterns around the circumference of the gastric corpus.

We recently described calbindin immunoreactivity in the myenteric plexus of the guinea-pig stomach. To study the neurochemical coding of calbindin D28 k (CALB)-containing myenteric neurones, the presence of calretinin (CALRET), choline acetyltransferase (ChAT), enkephalin (ENK), neuropeptide Y, serotonin (5-HT), somatostatin (SOM) and substance P(SP) was investigated immunohistochemically in colchicine-treated preparations. Nitric oxide synthase-containing neurones were detected by NADPH-diaphorase histochemistry. In addition, we investigated the neurone distribution patterns around the gastric corpus. Most CALB neurones were ChAT positive. ChAT/CALB neurones were either CALRET (ca 75%) or 5-HT positive and most contained in addition SP and/or ENK. All 5-HT neurones contained CALB. CALB labelled on average 2.3, 4.8 and 7.5 neurones per ganglion at the lesser curvature, in the central region and the greater curvature, respectively, which indicated a preferential localisation at the greater curvature. Compared to the total number of myenteric neurones, the proportion of CALB neurones increased significantly from the lesser curvature (6%) towards the greater curvature (18%). This shift, although observed for most ChAT/CALB-positive populations, was most prominent for the ChAT/CALB/CALRET/SP/ENK-encoded neurones. SOM-positive and ChAT-only encoded neurones were preferentially located at the lesser curvature. The remaining ten neurochemically defined populations did not exhibit an uneven distribution. The colocalisation of CALB with CALRET or 5-HT is specific for myenteric neurones in the stomach and represents one significant difference to the neurochemical code of CALB neurones in the guinea-pig intestine. The functional significance of the unevenness of neurone distribution along the circumference of the gastric corpus remains to be studied.

Animals↗
PubMed2001

Projections of excitatory and inhibitory motor neurones to the circular and longitudinal muscle of the guinea pig colon.

The aim of this study was to identify myenteric pathways to the circular and longitudinal muscle of the guinea pig proximal colon. To identify excitatory and inhibitory muscle motoneurones, we applied the neuronal retrograde tracer DiI onto the circular or longitudinal muscle layer and performed additional immunohistochemistry for nitric oxide synthase (NOS) and choline acetyltransferase (ChAT). On average 166 +/- 81 circular muscle motoneurones (CMMN) and 100 +/- 74 longitudinal muscle motoneurones (LMMN) were labelled by DiI tracing. Myenteric pathways innervating the muscle were either ascending (DiI-labelled neurones with oral projections) or descending (DiI-labelled neurones with anal projections). The circular muscle was preferentially innervated by ascending pathways (66.0 +/- 9.1%). Most ascending CMMN were ChAT-positive (87.2 +/- 8.5%), whereas descending CMMN were mainly NOS-positive (82.3 +/- 14.6%). Most ascending (62.2 +/- 11.1%) and descending (82.0 +/- 12.5%) CMMN had circumferential projection preferences (circumferential projections were longer than projections along the longitudinal gut axis). In contrast to the polarised projections to the circular muscle, the longitudinal muscle was equally innervated by ascending (46.2 +/- 15.1%) and descending (53.9 +/- 15.1%) neurones. Ascending and descending pathways to the longitudinal muscle consisted predominantly of ChAT-positive neurones (98.1 +/- 1.9% and 68.0 +/- 8.5%, respectively), and both pathways had prominent longitudinal projection preferences. Only 25.5% of the descending LMMN were NOS-positive. In conclusion, the circular muscle in the proximal colon is innervated by descending inhibitory (NOS-positive neurones) and ascending excitatory (ChAT-positive neurones) pathways. In contrast, the longitudinal muscle is primarily innervated by ascending and descending excitatory motoneurones, and only a small proportion of the descending pathway consisted of inhibitory motoneurones.

Animals↗