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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 333 (1986), S. 393-399 
    ISSN: 1432-1912
    Keywords: Enteric neurons ; Mucosal transport ; Noradrenaline ; Somatostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Noradrenaline (NA) and somatostatin (SOM) stimulate intestinal water and ion absorption and are found in mucosal nerve fibres and nerve terminals in submucous ganglia of the guinea-pig small intestine. As the main projection of submucous neurons is to the mucosa, NA and SOM might alter mucosal transport either by a direct effect on the epithelium or indirectly, by affecting submucous neurons. In this study these two possible sites of action of NA and SOM have been investigated in mucosa-submucosa preparations of guinea-pig ileum. In addition, the actions of NA and SOM on the secretory responses caused by stimulation of different populations of submucous neurons have been studied. The stimulants of secretion used were a nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10−5 M), 5-hydroxytryptamine (5-HT, 10−7 M) and electrical field stimulation (EFS), which activate cholinergic, noncholinergic and mixed populations of submucous secretomotor neurons, respectively. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (I sc) was measured as an indication of net active ion transport across the tissue. NA (≥10−8 M) and SOM (〉10−10 M) each caused a decrease in I sc, indicating a net increase in ion absorption. The NA response was abolished and the magnitude of the SOM response was reduced to 20% by tetrodotoxin (10−7 M). DMPP, 5-HT and EFS each stimulated nerves that increased I sc and each of these responses was significantly diminished by NA and SOM; for both NA and SOM the decrease in the DMPP response was significantly greater than the decrease observed in the response to carbachol (10−6 M). Phentolamine (10−6 M) abolished all of the effects of NA but caused no change in the SOM effects. These studies have shown that NA and SOM cause similar changes in net ion transport, that their actions are primarily on submucous secretomotor neurons and that NA and SOM can diminish the responses to stimulation of both cholinergic and noncholinergic submucous neurons. In this tissue it is also known that SOM coexists with NA in noradrenergic nerve terminals in the submucosa. However, when applied together, NA and SOM caused no greater decrement in the carbachol and 5-HT responses than would be predicted by adding the separate effects of NA and SOM. Hence there was no obvious interaction between NA and SOM effects on mucosal transport.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 328 (1985), S. 446-453 
    ISSN: 1432-1912
    Keywords: Substance P ; Enteric neurons ; Autonomic nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The sites of action and possible roles of substance P in contracting the circular muscle of the guinea-pig ileum were studied using two analogues of substance P that act as antagonists of some of its actions. These ared-Arg1,d-Pro2,d-Trp7,9, Leu11-substance P andd-Pro2,d-Trp7,9-substance P, referred to by the single letter amino acid codes for the substituting amino acids as (RPWWL)-SP and (PWW)-SP, respectively. Records of circular muscle activity were taken from strips of intestine free of mucosa and submucosa and from rings with all layers of intestine intact. Substance P was equally effective in contracting the circular muscle strips as it was in contracting the longitudinal muscle. The contractions of strips were not blocked by hyoscine (2×10−6 M) or tetrodotoxin (6×10−7 M), but were substantially reduced by (RPWWL)-SP (6.7×10−6 M) or (PWW)-SP (2×10−5 M). In contrast, contractions of the circular muscle of whole rings of intestine elicited by low concentrations of substance P (4×10−7M) were blocked by hyoscine or tetrodotoxin but notreduced by the substance P antagonists in the concentrations referred to above. These observations indicate that the antagonists are effective at receptors for substance P on the muscle, but not at substance P receptors on enteric cholinergic nerves. Transmural stimulation of strips of circular muscle or of intestinal rings in the presence of hyoscine evoked contractions that were blocked by tetrodotoxin. These hyoscineresistant, nerve-mediated contractions could be elicited by single pulses in the strips. The contractions were reduced to less than 20% of original amplitude by (RPWWL)-SP (6.7×10−6M). Reflex contractions of the circular muscle recorded on the oral side of a distension stimulus had a low-threshold, hyoscine-sensitive and a high-threshold, hyoscine-insensitive, component. The low threshold component was unaffected by the substance P antagonists whereas the high threshold component was depressed. It is concluded that substance P nerves are effective in transmitting to the circular muscle, that they are final nerves in non-cholinergic excitatory reflexes, and that the substance P antagonist analogues can be used to distinguish actions of substance P at neural and muscle receptors.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 329 (1985), S. 382-387 
    ISSN: 1432-1912
    Keywords: Substance P ; Enteric neurons ; Mucosal transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The action of substance P (SP) on mucosal ion transport has been investigated in the guinea-pig small intestine. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (I sc) was measured as an indication of net ion transport across the tissue. SP (〉10−10 M) added to the submucosal side of the tissue caused a transient increase in I sc. Tetrodotoxin (TTX, 10−7 M) decreased the maximum SP response to 11% of the control value. TTX completely inhibited the response to electrical field stimulation but had no effect on I sc increases due to carbachol or theophylline. In the presence of hyoscine (10−7 M) the SP response was reduced to 42% of the control value, but hyoscine had no effect on the TTX-resistant SP response. Mepyramine (10−6 M) had no significant effect on the SP response. These results suggest that SP alters mucosal ion transport by stimulation of cholinergic and non-cholinergic nerves in the mucosa-submucosa. A small part of the SP response appears to be due to a direct action on epithelial cells. The SP antagonist (d-Arg1, d-Pro2, d-Trp7.9, Leu11)-SP decreased the magnitude of the TTX-resistant SP response, and caused a decrease of similar magnitude in the total SP response. These results imply that the major component of the SP response, which is due to an action on neurons, is unaffected by this antagonist. It is concluded that the SP receptors on epithelial cells are blocked by the antagonist and are different to the SP receptors on submucous neurons, which are not blocked by the antagonist.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 331 (1985), S. 260-266 
    ISSN: 1432-1912
    Keywords: Enteric neurons ; Serotonin ; Mucosal transport ; Substance P receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is known that the majority of the mucosal nerve fibres in the guinea-pig small intestine arise from submucous ganglia. There are a number of neurochemically distinct populations of nerve cells in these ganglia, approximately half of them being cholinergic. In these studies we have stimulated isolated preparations of mucosa and submucosa with electrical field stimulation (EFS), 5-hydroxytryptamine (5-HT) and the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) and monitored changes in ion transport. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (I sc) was measured as an indication of net ion transport across the tissue. EFS consisted of passing bipolar rectangular stimulus pulses through two platinum wires, one placed on each of the mucosal and submucosal sides of the tissue. EFS, 5-HT and DMPP each caused a transient increase inI sc. Tetrodotoxin (TTX) abolished all of the EFS response and the majority of the response observed with 5-HT or DMPP, suggesting that the action of these stimuli on the mucosa is primarily nerve-mediated. The TTX-sensitive responses to 5-HT (〉5×10−7 M) and DMPP consisted of two components, appearing with different latencies. The response to EFS also consisted of two components. Hyoscine abolished the first component of each of these responses and significantly reduced the amplitude of the second, by 40% (for EFS and 5-HT) and 84% (for DMPP). At lower 5-HT concentrations, only the later component was seen, and this was unaffected by hyoscine. These results suggest that the early component of each response is due to the release of acetylcholine from cholinergic nerves. The hyoscine-resistant responses to EFS and DMPP were reduced by a substance P antagonist (d-Arg1,d-Pro2,d-Trp7,9, Leu11), suggesting that these responses involve activation of substance P receptors in the mucosa. The studies suggest that EFS and 5-HT (〉5×10−7 M) stimulate both cholinergic and non-cholinergic nerves effectively, that 5-HT (10−8–5×10−7 M) preferentially stimulates non-cholinergic nerves and that DMPP preferentially stimulates cholinergic nerves.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0878
    Keywords: Submucous plexus ; Mucosa ; Muscularis mucosae ; Intestine, small ; Retrograde transport ; Dil ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Double-labelling immunohistochemistry and retrograde transport of the carbocyanine dye, DiI, were used to establish the pathways of submucous neurons to the mucosa of the guinea-pig small intestine. Following the application of DiI to a villus, DiI-labelled nerve cell bodies were found in the submucous plexus up to 8.3 mm circumferentially and 3.8 mm longitudinally. The size of each of the four characterised classes of submucous neurons was determined and their distributions and projections mapped. Cells characterised by vasoactive intestinal polypeptide immunoreactivity accounted for 52% of DiI-labelled cells and had the longest projections. Cells characterised by neuropeptide Y (19%) or by calretinin immunoreactivity (13% of all DiI-labelled neurons) had relatively short projections and cells with substance P immunoreactivity (20%) had intermediate lengths of projection. When DiI was applied directly to the submucous plexus, filled neurons of all classes had significantly shorter projections, indicating that they must run for considerable distances in other pathways to the mucosa, probably via the non-ganglionated plexus. On average, each villus is innervated by at least 70 submucous neurons. From quantitative estimates there are 9 submucous neurons per villus. Thus, each submucous neuron is likely to supply about 8 villi. This demonstrates a high degree of convergence and divergence in the innervation of the mucosa.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0878
    Keywords: Myenteric plexus ; Enteric nervous system ; Intestine, small ; Ultrastructure ; Innervation, of intestinal muscle ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The tertiary component of the myenteric plexus consists of interlacing fine nerve fibre bundles that run between its principal ganglia and connecting nerve strands. It was revealed by zinc iodide-osmium impregnation and substance P immunohistochemistry at the light-microscope level. The plexus was situated against the inner face of the longitudinal muscle and was present along the length of the small intestine at a density that did not vary markedly from proximal to distal. Nerve bundles did not appear to be present in the longitudinal muscle as judged by light microscopy, although numberous fibre bundles were encountered within the circular muscle layer. At the ultrastructural level, nerve fibre bundles of the tertiary plexus were found in grooves formed by the innermost layer of longitudinal smooth muscle cells. In the distal parts of the small intestine, some of these nerve fibre bundles occasionally penetrated the longitudinal muscle coat. Vesiculated profiles in nerve fibre bundles of the tertiary plexus contained variable proportions of small clear and large granular vesicles; they often approached to within 50–200 nm of the longitudinal smooth muscle cells. Fibroblast-like cells lay between strands of the tertiary plexus and the circular muscle but were never intercalated between nerve fibre varicosities and the longitudinal muscle. These anatomical relationships are consistent with the tertiary plexus being the major site of neurotransmission to the longitudinal muscle of the guinea-pig small intestine.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0878
    Keywords: Myenteric plexus ; Smooth muscle ; Organotypic culture ; Ultrastructure ; Intestine, small ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract External muscle and myenteric plexus from the small intestine of adult guinea-pigs were maintained in vitro for 3 or 6 days. Myenteric neurons and smooth muscle cells from such organotypic cultures were examined at the electron-microscopic level. An intact basal lamina was found around the myenteric ganglia and internodal strands. Neuronal membranes, nuclei and subcellular organelles appeared to be well preserved in cultured tissues and ribosomes were abundant. Dogiel type-II neurons were distinguishable by their elongated electron-dense mitochondria, numerous lysosomes and high densities of ribosomes. Vesiculated nerve profiles contained combinations of differently shaped vesicles. Synaptic membrane specializations were found between vesiculated nerve profiles and nerve processes and cell bodies. The majority of nerve fibres were well preserved in the myenteric ganglia, in internodal strands and in bundles running between circular muscle cells. No detectable changes were found in the ultrastructure of the somata and processes of glial cells. Longitudinal and circular muscle cells from cultured tissue had clearly defined membranes with some close associations with neighbouring muscle cells. Caveolae occurred in rows that ran parallel to the long axis of the muscle cells. These results indicate that the ultrastructural features of enteric neurons and smooth muscle of the guinea-pig small intestine are well preserved in organotypic culture.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 247 (1987), S. 377-384 
    ISSN: 1432-0878
    Keywords: Enkephalin ; Gastrin releasing peptide ; Neuropeptide Y ; Somatostatin ; Substance P ; Vasoactive intestinal peptide ; Enteric nervous system ; Intestine, small ; Dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The projections of nerve fibres with immunoreactivity for the peptides enkephalin (ENK), gastrin-releasing peptide (GRP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and vasoactive intestinal peptide (VIP) were studied in canine small intestine by analysing the consequences of lesions of intrinsic and extrinsic nerves. Of peptides present in fibres supplying myenteric ganglia, GRP, SOM and VIP were in anally directed nerve pathways, whereas ENK and NPY were in orally directed pathways. Pathways ran for up to about 30 mm. SP fibres ran for short distances in both directions in the myenteric plexus. The circular muscle was supplied with ENK, NPY, SP and VIP fibres arising from the myenteric ganglia, whereas most mucosal SP and VIP fibres were deduced to arise from submucous ganglia. There were projections of fibres reactive for ENK, GRP, SOM, SP and VIP from myenteric ganglia to submucous ganglia. Antibodies to tyrosine hydroxylase were used to locate noradrenaline nerve fibres supplying the intestine; these fibres all disappeared when extrinsic nerves running through the mesentery to the small intestine were cut. It is deduced that there is an ordered pattern of projections of peptide-containing fibres in the canine intestine.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0878
    Keywords: Calcitonin gene-related peptide ; Cholecystokinin ; Choline acetyltransferase ; Neuropeptide Y ; Somatostatin ; Enteric nervous system ; Intestine, small ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Antisera to neuropeptide Y (NPY) gave an intense immunohistochemical reaction of certain nerve cells in the myenteric and submucous plexuses of the guinea-pig small intestine. Each nerve cell had up to 20 branching, tapering processes that were less than ∼50 μm long and a long process that could be followed for a considerable distance. This morphology corresponds to that of the type-III cells of Dogiel. The long process of each myenteric cell ran through the circular muscle to the submucosa, and in most cases the process could be traced to the mucosa. The submucous nerve cell bodies also had processes that extended to the mucosa. These cell bodies, in both plexuses, also stained with antisera raised against calcitonin generelated peptide (CGRP), cholecystokinin (CCK), choline acetyltransferase (ChAT) and somatostatin (SOM), but did not stain with antibodies against enkephalin, substance P or vasoactive intestinal peptide. Thus, it has been possible for the first time to trace the processes of chemically specified neurons through the layers of the intestinal wall and to show by a direct method that CGRP/CCK/ChAT/NPY/ SOM myenteric and submucous nerves cells provide terminals in the mucosa.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0878
    Keywords: Enteric nervous system ; Intestine, small ; Nerves, degeneration ; Neuronal connections ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A quantitative ultrastructural study was made of the neuntes forming the deep muscular and circular muscle plexuses of the guinea-pig small intestine following microsurgical lesions designed to interrupt intrinsic and extrinsic nerve pathways within the intestinal wall. Removal of a collar of longitudinal muscle with attached myenteric plexus from the circumference of a segment of small intestine resulted in the subsequent disappearance of 99.3% of neurites in the underlying circular muscle. The few surviving neurites in the deep muscular plexus and circular muscle disappeared completely from lesioned segments that were, in addition, extrinsically denervated surgically. These results indicate that the majority of nerve fibres in the deep muscular and circular muscle plexuses of the guinea-pig small intestine is intrinsic to the intestine and originates from nerve cell bodies located in the overlying myenteric plexus. At the light-microscopic level, nerve bundles were traced from the myenteric plexus to the circular muscle.
    Type of Medium: Electronic Resource
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