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At least 19 recordsLinked to original sources

Deficient neurogenic innervation of the myenteric plexus with normal submucous plexus involving the entire small and large bowel.

A newborn presented with a picture of intestinal obstruction. Multiple biopsies of the small and large bowel showed an unusual neurogenic innervation. The myenteric plexus of Auerbach was severely depleted of ganglion cells and nerve fibers, while the submucous plexus of Meissner was normally innervated. An ileostomy failed to function and extended trial with experimental smooth muscle stimulant (Cisapride) was equally ineffective. The patient was finally treated by a myectomy from the duodenum to the descending colon with a sigmoid colostomy. This procedure, coupled with a Nissen fundoplication, stopped the vomiting and allowed normal defecation through the colostomy. The patient is presently taking increasing increments of oral fluids with a concomitant decrease in the volume of parenteral nutrition. The myectomy initiated marked hypertrophy of the muscularis mucosa. Could this muscular hypertrophy account for the improvement in bowel function? Possible etiology will be discussed. We caution that rectal submucosal suction biopsy alone may be misleading if normal ganglion cells and nerve fibers are found, yet the patient's clinical symptoms fail to improve. A full thickness bowel wall biopsy is then recommended.

Ganglia, Parasympathetic↗

[The external submucous plexus (Schabadasch) in the small intestine of the swine. I. Form, structure and connections of ganglia and nerve cells].

1. There are described principles of organization of the plexus submucous externus (Schabadasch) in the small intestine of the pig. They can be summarized under the term of polarization of nerve cells. 2. The principle of polarization is realized for instance by the formation of type I and type II cell aggregates and by the specific course of the processes of both cell types. 3. These criteria of organization which are much clearer in the pig than in other animals, recommend the plexus Schabadasch of the pig as a suitable model for further investigations.

Animals↗

Studies on the intrinsic nervous system of the wild rodent Calomys callosus digestive tract. II. The submucous plexus.

The submucous plexus of the normal small and large intestine of Calomys callosus was studied by NADH and AChE histochemical techniques and by transmission and scanning electron microscopy. The plexus contains (X +/- SD) 7,488 +/- 293 neurons/cm2 in the duodenum, 5,611 +/- 836 in the jejunum, 2,741 +/- 360 in the ileum, 3,067 +/- 179 in the cecum, and 3,817 +/- 256 in the proximal colon. No ganglia or nerve cell bodies were seen in the esophagus, stomach, distal colon or rectum. The neurons are pear-shaped with a round or oval nucleus and the neuronal cell profile areas were larger in the large intestine than in the small intestine. Most of the neurons display intense AChE activity in the cytoplasm. AChE-positive nerve fibers are present in a primary meshwork of large nerve bundles and in a secondary meshwork of finer nerve bundles. At the ultrastructural level, the ganglia are irregular in shape and covered with fibroblast-like cells. The nucleoplasm of the neurons is finely granular with a few condensations of chromatin attached to the nuclear envelope. In the neuropil numerous varicosities filled with vesicles of different size and electron densities are seen. The pre- and post-synaptic membrane thickenings are asymmetric. Characteristic glial cells with oval nuclei and few organelles are numerous. These data provide a detailed description of this submucosal meshwork.

Acetylcholinesterase↗

Dissection of the external and internal submucous plexuses of the pig small intestine.

The submucous plexus of large mammals like dog, horse, cow, sheep, pig and man consists of more than one easily identified plexus. The divisions of the submucous plexus are known as the external submucous plexus and the internal submucous plexus. Recently findings have shown that there exists functional differences between the neuronal populations in the subdivisions of the submucous plexus in the small intestine of pigs. We report here how to obtain whole mounts of the submucous plexus containing both the internal and the external submucous plexus. The whole mounts from the submucous plexus of the pig contains almost no muscle and can be used in intracellular neuronal studies without adding nifedipine or equivalent L-type Ca2+ channel blockers to inhibit the contractions of the smooth muscle.

Animals↗

Contractions of the guinea-pig ileum evoked by stimulation of the submucous plexus.

Neural pathways from the submucous plexus to the longitudinal muscle of an adjacent segment of isolated guinea-pig ileum were studied. It was found that electrical field stimulation of a strip of submucosa-submucous plexus produced frequency-dependent longitudinal contractions of an intact segment of intestine lying oral to the point of stimulation. The responses were reduced to less than 10% of control by tetrodotoxin, atropine, morphine and chymotrypsin and by desensitization to substance P (SP). The responses were only inhibited by one-third by hexamethonium and were not affected by desensitization to 5-hydroxytryptamine. The effect of desensitization to SP was reversible, but the effect of chymotrypsin was irreversible. SP-induced desensitization and chymotrypsin did not inhibit the twitch response produced by field stimulation of the whole ileal segment. The same results were observed with preparations made from ileal segments that had been extrinsically denervated. The results suggest that intrinsic neurons with processes in the submucous plexus can excite cholinergic and SP-containing neurons in the myenteric plexus, thereby causing the longitudinal muscle to contract.

Animals↗

Ultrastructural study of nerve terminals in the submucous plexus and mucous membrane after extirpation of the myenteric plexus.

An attempt is made to separate in the submucous plexus and mucous membrane of the chronically isolated intestine of the cat the fibers originating from the myenteric plexus and those originating from the submucous plexus by secondary degeneration after the extirpation of the myenteric plexus. A considerable part of the nerve processes in the submucous plexus originate from the cells of the myenteric ganglia and establish direct synaptic relationships between the ganglion cells, or are very close to the blood vessels. The numerous intact synapses between the different nerve elements in the submucous plexus point to local reflex connexions within the plexus itself. The degeneration of sub-epithelial nerve elements, containing always clear and dense-core (1,000-1,200 A in diameter) vesicles besides the numerous intact nerve elements, might indicate the presence of real sensory nerve processes in this layer. The terminal fibers remaining intact after removal of the myenteric plexus contain numerous medium-sized dense-core vesicles in potassium permanganate-fixed material. This suggests that there are cells containing 5-hydroxytryptamine in the submucous plexus.

Animals↗

Neuronal populations in the submucous plexus of the human colon.

The submucous plexus of the human distal colon was studied in order to determine whether or not it contains two or more ganglionated plexuses which can be separately identified. Nerve cells were visualised in sections through the wall of the distal colon, and in wholemount preparations of laminae from the submucous plexus by staining for NADH-diaphorase activity. The submucous plexus appeared to contain three identifiable plexuses: Henle's plexus was located adjacent to the circular muscle layer, Meissner's plexus was located adjacent to the muscularis mucosae and a third intermediate plexus was found which lay closer to the muscularis mucosae than to the circular muscle. In Henle's plexus, there were fewer smaller neurons than in the other plexuses: 15.1% had an area less than 180 microns 2, while in the intermediate plexus and in Meissner's plexus the equivalent figures were 43.1% and 43.2%, respectively. In Meissner's plexus, approximately half the ganglia were associated with single fibre tracts and half with two or more fibre tracts, but in the intermediate plexus and Henle's plexus, approximately three quarters of the ganglia were associated with single fibre tracts and the remaining quarter with multiple tracts.

Adult↗

Electrophysiological properties of neurones in the internal and external submucous plexuses of newborn pig small intestine.

1. Intracellular microelectrodes were used to identify three major electrophysiological categories of neurone in both the internal and external submucous plexuses of the porcine small intestine. 2. Two classes of neurone with a long-lasting after-hyperpolarization following their action potential were differentiated by the presence or absence of fast excitatory synaptic inputs (EPSPs) and were termed AH neurones. S neurones received fast EPSPs but did not display after-hyperpolarizations. 3. The mean resting membrane potentials of the three groups of neurones showed a similar trend in both plexuses, with significantly higher values for the two populations of AH neurone than for S neurones. No significant variation of input resistance with cell type was detected. Neuronal input resistance was significantly greater in the internal submucous plexus than in the external submucous plexus. 4. Over 80% of AH neurones in the internal submucous plexus displayed fast EPSPs but a similar percentage of AH neurones in the external submucous plexus did not show fast EPSPs. S neurones constituted 60% of cells studied in the internal submucous plexus but less than 30% of the cell population in the external submucous plexus. 5. This study of porcine submucous neurones has revealed both similarities and differences to previous work in the guinea-pig small intestine. The most contrasting features are the relative abundance and subclassification of AH neurones in the pig in addition to the apparent paucity of slow synaptic potentials. The differences in the neuronal profiles of the internal and external submucous plexuses may reflect a differentiation of function between the two enteric nerve networks.

Animals↗

Development of the submucous plexus in the large intestine of the mouse.

In the small intestine of both embryonic birds and mammals, neuron precursors aggregrate first at the site of the myenteric plexus, and the submucous plexus develops later. However, in the large intestine of birds, the submucosal region is colonised by neural-crest-derived cells before the myenteric region (Burns and Le Douarin, Development 125:4335-4347, 1998). Using antisera that recognize undifferentiated neural-crest-derived cells (p75NTR) and differentiated neurons (PGP9.5), we examined the colonisation of the murine large intestine by neural-crest-derived cells and the development of the myenteric and submucosal plexuses. At E12.5, when the neural crest cells were migrating through and colonising the hindgut, the hindgut mesenchyme was largely undifferentiated, and a circular muscle layer could not be discerned. Neural-crest-derived cells migrated through, and settled in, the outer half of the mesenchyme. By E14.5, neural-crest-derived cells had colonised the entire hindgut; at this stage the circular muscle layer had started to differentiate. From E14.5 to E16.5, p75NTR- and PGP9.5-positive cells were observed on the serosal side of the circular muscle, in the myenteric region, but not in the submucosal region. Scattered, single neurons were first observed in the submucosal region around E18.5, and groups of neurons forming ganglia were not observed until after birth. The development of the enteric plexuses in the murine large intestine therefore differs from that in the avian large intestine.

Animals↗

Fine structure of the myenteric and submucous plexuses in the stomach of a coral fish, Chelmon rostratus Cuvier.

The fine structure of the teleostean myenteric and submucous plexuses has been studied in the stomach of the coral fish, Chelmon rostratus Cuvier. The myenteric plexus is a prominent loose mesh containing nerve cells, myelinated and unmyelinated axon profiles, vesiculated axon profiles, Schwann cells, collagen and capillaries. Unmyelinated axons greatly outnumber the myelinated ones. Vesiculated axon profiles were uncommon, and synapses were rarely observed. Compared with the myenteric plexus, the submucous plexus was more modest in size; it was devoid of nerve cells and myelin sheaths were only occasionally seen.

Animals↗

Morphometric quantification of normal submucous plexus in the distal rectum of adult healthy volunteers.

OBJECTIVE: Inadequate morphometric characterization of the normal adult submucous plexus has precluded the diagnosis of colonic dysganglionoses associated with constipation, such as intestinal neuronal dysplasia type B (IND B). The internal submucous plexus (Meissner plexus) was morphometrically quantified in adult healthy volunteers. DESIGN: Open, prospective morphometric study in balanced groups of female and male volunteers. PARTICIPANTS: Thirty-seven adult healthy male and female volunteers with normal bowel function and no history of gastrointestinal disease. METHODS: Four jumbo rectal biopsies (3-5 mm3) were taken 5 and 10 cm above the pectinate line. Two expert gastrointestinal pathologists assessed biopsy sections after specific nerve cell staining for lactic dehydrogenase, nitric oxide synthase and acetylcholinesterase, mainly for characteristics of ganglia and nerve cells in the submucous plexus. RESULTS: No healthy individual demonstrated over 20% of submucosal ganglia as giant ganglia or more than four giant ganglia per 30 sections (the morphometric criteria for IND B). Single submucosal nerve cells and ganglion numbers halved between 10 and 5 cm above the pectinate line, but there were no age or gender differences. The biological variability of nerve cell and ganglion density in the submucous plexus was large. CONCLUSIONS: Healthy adults show less than 20% of submucosal ganglia as giant ganglia and no more than four giant ganglia per 30 rectal biopsy sections. There is therefore no overlap with the histomorphological criteria of IND B. These data therefore support the specificity of the previously defined criteria for IND B in adults.

Adult↗

Inhibitory synaptic potentials resulting from alpha 2-adrenoceptor activation in guinea-pig submucous plexus neurones.

Intracellular recordings were obtained from neurones of the guinea-pig submucous plexus. Inhibitory synaptic potentials (i.p.s.p.s) were compared with hyperpolarizations evoked by brief, local applications of noradrenaline and by superfusion with adrenoceptor agonists. Hyperpolarizing potentials elicited by brief applications of noradrenaline were similar to the i.p.s.p. in latency of onset, amplitude, time course, conductance increase, reversal potential and ionic dependence. Both responses were blocked by low concentrations of Ba2+ and quinine. 6-hydroxydopamine selectively and irreversibly abolished the i.p.s.p. and resulted in a complete loss of catecholamine fluorescent nerve fibres in the submucous plexus. The alpha 2-adrenoceptor antagonists, phentolamine, yohimbine and RX781094, reversibly blocked the i.p.s.p. and the noradrenaline hyperpolarization. Prazosin, propranolol, atropine and naloxone had no effect on these responses. Superfusion with noradrenaline and clonidine produced dose-dependent membrane hyperpolarizations. Noradrenaline and clonidine dose-hyperpolarization curves were shifted to the right in a parallel fashion by alpha 2-adrenoceptor antagonists. Determination of the dissociation equilibrium constants for phentolamine, yohimbine and RX781094 showed that the hyperpolarization produced by noradrenaline perfusion is due to alpha 2-adrenoceptor activation. It is concluded that the release of noradrenaline from sympathetic nerves activates post-synaptic alpha 2-adrenoceptors, resulting in the K+ conductance increase which underlies the i.p.s.p. in submucous plexus neurones.

Action Potentials↗

Ultrastructural localisation of substance P, vasoactive intestinal peptide and somatostatin immunoreactivities in the submucous plexus of guinea pig ileum.

The submucous neurons, especially those related to the lymphatic vessels, together with their associated synapses, were studied ultrastructurally with respect to their immunoreactivities for 3 types of neuropeptides, namely substance P (SP), vasoactive intestinal peptide (VIP) and somatostatin (SOM). With the antibodies directed against the 3 types of neuropeptides, a variable number of submucous neurons including those contacting the lymphatic vessels were immunostained. Based on the immunoreactivities and synaptic relations with the submucous neurons contacting the lymphatic vessels, at least 4 types of synaptic relations with the submucous neurons contacting the lymphatic vessels, at least 4 types of synaptic configurations were observed: immunopositive terminals with positive neurons, immunopositive terminals with negative neurons, immunonegative terminals with positive neurons and immunonegative terminals with negative neurons. All 4 types of synaptic configurations were observed in SP and VIP-immunostained specimens, with the exception of type 3 which was not encountered in samples immunoreacted for SOM. When the proportions of all 4 types of peptidergic immunopositive terminals contacting the lymphatic vessel-associated neurons were totalled, the value exceeded 100%, suggesting the coexistence of 2 or more neuropeptides in the same terminals. Furthermore, some immunoreactive axon terminals made direct synaptic contacts with positive neurons suggesting the formation of the so-called 'peptide neuron chain'. It is speculated from this study that the submucous neurons receive multiple peptidergic inputs. The various synaptic contacts would imply a complicated reflex pathway in the submucous plexus.

Animals↗

A non-adrenergic, non-cholinergic slow inhibitory post-synaptic potential in neurones of the guinea-pig submucous plexus.

1. Intracellular recordings were made from neurones in the submucous plexus of guinea-pig ileum and caecum. The responses to electrical stimulation of fibre strands entering the nodes of the plexus were studied. 2. Stimuli comprising trains of pulses (20 Hz, 1-5 s) produced nicotinic excitatory post-synaptic potentials (fast e.p.s.p.s), an adrenergic inhibitory post-synaptic potential (i.p.s.p.), a slow excitatory post-synaptic potential (slow e.p.s.p.) and a fourth, hitherto unnoticed, slow hyperpolarization which followed the slow e.p.s.p. All these responses were abolished by tetrodotoxin or solutions containing a low calcium concentration. 3. The slow hyperpolarization (slow i.p.s.p.) was examined in the presence of blockers of the nicotinic and adrenergic responses, and in conditions in which the slow e.p.s.p. was prevented by desensitizing concentrations of substance P or vasoactive intestinal polypeptide. The slow i.p.s.p. was unaffected by prazosin (0.1-1 microM), propranolol (0.1-1 microM), atropine (1 microM) or naloxone (1 microM). 4. The amplitude and duration of the slow i.p.s.p. increased with increasing numbers of stimulus pulses; it had an amplitude of 17 mV and a duration of 70 s when evoked by a stimulus of 20 Hz for 3 s. 5. The slow i.p.s.p. was associated with a decrease in the input resistance of the cell. It reversed polarity at -90 mV in 4.7 mM-potassium and the extrapolated reversal potential in 0.47 mM-potassium was -145 mV; these findings indicate that the slow i.p.s.p. results from an increase in membrane potassium conductance. 6. The slow i.p.s.p. could still be recorded from submucous plexus neurones in segments of ileum which had been extrinsically denervated 6-11 days previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Organization of the enteric nervous system in the human colon demonstrated by wholemount immunohistochemistry with special reference to the submucous plexus.

To demonstrate the normal topography and structure of the enteric nervous system (ENS) in the human colon, the colonic wall of patients (n = 10, mean age 66.3 years), who underwent abdominal surgery unrelated to intestinal motility disorders, was submitted to wholemount immunohistochemistry. The specimens were stretched out and separated into the tunica muscularis, the outer and inner portion of the tela submucosa and the tunica mucosa. Prior to the application of the neuronal marker Protein Gene Product (PGP) 9.5, the laminar preparations were pretreated with the maceration agent KOH. The plexus myentericus was composed of prominent ganglia and interconnecting nerve fiber strands (NFS) forming a polygonal network, which was denser in the descending than in the ascending colon. Nerve cells were observed within the ganglia as well as in primary, secondary and tertiary NFS. The latter ramified into the adjacent smooth muscle layers, which contained the aganglionated plexus muscularis longitudinalis and circularis. The submucous plexus comprised three nerve networks of different topography and architecture: the delicate plexus submucosus extremus consisted of parallel orientated NFS with isolated nerve cells and small ganglia and was located at the outermost border of the tela submucosa adjacent to the circular muscle layer. The plexus submucosus externus was closely associated with the plexus submucosus extremus and composed of larger ganglia and thicker NFS. The plexus submucosus internus was situated adjacent to the lamina muscularis mucosae and formed a network with denser meshes but smaller ganglia and NFS than the plexus submucosus externus. The NFS of the aganglionated plexus muscularis mucosae followed the course of the smooth muscle cells of the lamina muscularis mucosae. The honeycomb-like network of the plexus mucosus was located within the lamina propria mucosae and divided into a subglandular and a periglandular portion. Single and accumulated nerve cells were observed within the plexus mucosus as a regular feature. The findings confirm the complex structural organisation of the ENS encountered in larger mammals, in particular the subdivision of the submucous plexus into three different compartments. PGP 9.5-immunohistochemistry applied to wholemount preparations comprehensively visualized the architecture of the intramural nerve plexus in human colonic specimens. In addition to conventional cross-sections, this technique allows a subtle assessment and classification of structural alterations of the ENS in patients with colorectal motor disorders.

Aged↗

Transient expression of neuronal nitric oxide synthase by neurons of the submucous plexus of the mouse small intestine.

Although neurons containing neuronal nitric oxide synthase (NOS) are abundant in the myenteric plexus of the small intestine of all mammalian species examined to date, NOS-containing neurons are sparse in the submucous plexus, and there does not appear to be an innervation of the mucosa by nerve fibres containing NOS. In this study, we used immunohistochemical techniques to examine the presence of neuronal NOS in the mouse intestine during development. At embryonic day 18 and postnatal day 0 (P0), about 50% of the neurons in the submucous plexus of the small intestine showed strong immunoreactivity to NOS, and NOS-immunoreactive nerve fibres were present in the mucosa. By P7, there was a gradation in the intensity of NOS immunostaining exhibited by submucosal neurons, varying from intense to extremely weak. During subsequent development, the proportion of submucous neurons showing NOS immunoreactivity decreased, and immunoreactive nerve fibres were no longer observed in the mucosa. In adult mice, NOS neurons comprised only 3% of neurons in the submucous plexus, which is significantly less than at P0. In contrast to the submucous plexus, the percentage of neurons that showed NOS immunoreactivity in the myenteric plexus did not change significantly during development.

Aging↗

Somatostatin increases an inwardly rectifying potassium conductance in guinea-pig submucous plexus neurones.

1. Intracellular recordings were made from neurones in the submucous plexus of the guinea-pig caecum and ileum. 2. Somatostatin hyperpolarized more than 90% of the neurones. The lowest effective concentration was 300 pM and the maximum hyperpolarization (about 30-35 mV) was caused by 30 nM. Under voltage clamp at -60 mV, somatostatin caused outward currents which reached a maximum of 350-700 pA. 3. The hyperpolarization or outward current reversed polarity at a membrane potential (about -90 mV in control solutions) which changed according to the logarithm of the external potassium concentration. 4. The somatostatin current showed inward rectification; when the inward rectification of the resting membrane was prevented by extracellular caesium or rubidium, the inward rectification of the somatostatin current also disappeared. 5. A potassium conductance with the same properties was increased by alpha 2-adrenoceptor agonists and by delta-opioid receptor agonists; however, the effects of somatostatin were unaffected by antagonists at alpha 2- or delta-receptors. The somatostatin analogue, cyclo-aminoheptanoyl-Phe-D-Trp-Lys-(benzyl)Thr, also did not antagonize the actions of somatostatin. 6. The hyperpolarization (or outward current) was unaffected by forskolin, cholera toxin, sodium fluoride, phorbol esters or intracellular application of adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S). However, when the recording electrode contained guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) the hyperpolarizations reversed only partially when somatostatin application was discontinued, and repeated applications caused the membrane potential to approach and remain close to the potassium equilibrium potential. 7. It is concluded that somatostatin increases the conductance of a set of inwardly rectifying potassium channels in submucous plexus neurones. The coupling between somatostatin receptor and ion channel involves a guanosine 5'-triphosphate-binding protein, but is not likely to result from changes in intracellular levels of cyclic adenosine 3',5'-monophosphate.

Action Potentials↗

Peptide-containing neurons in different regions of the submucous plexus of human sigmoid colon.

Specimens of the sigmoid colon were obtained from male and female patients (n = 11) with carcinoma of the colon or rectum and studied immunohistochemically for vasoactive intestinal polypeptide-, somatostatin-, substance P-, neuropeptide Y-, calcitonin gene-related peptide-, met- and leu-enkephalin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-containing nerves. In the subdivisions of the submucous plexus (namely, Schabadasch's, Meissner's, and the intermediate plexuses), substance P- and vasoactive intestinal polypeptide-immunoreactive nerve fibers were the most numerous, and equal densities of these nerves were found in all three layers. In contrast, few neuropeptide Y-, met-enkephalin-, leu-enkephalin-, calcitonin gene-related peptide-, somatostatin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-immunoreactive nerves were found in these regions. The nerve cell bodies of the submucous plexus contained vasoactive intestinal polypeptide, substance P, leu-enkephalin, somatostatin, and 5-hydroxytryptamine but not neuropeptide Y, met-enkephalin, calcitonin gene-related peptide, and dopamine beta-hydroxylase. Vasoactive intestinal polypeptide-containing nerve cell bodies were found in all three subdivisions. Substance P-, leu-enkephalin-, and somatostatin-immunoreactive nerve cell bodies were found in Schabadasch's plexus and the intermediate region of the submucous plexus, but they were absent from Meissner's plexus; 5-hydroxytryptamine-containing nerve cell bodies were only observed in Schabadasch's plexus. The possible function of the neuropeptide-, dopamine beta-hydroxylase-, and 5-hydroxytryptamine-containing neurons in the different layers of the submucous plexus is discussed.

Adult↗