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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Peptides 2 (1981), S. 119-122 
    ISSN: 0196-9781
    Keywords: 5-Hydroxytryptamine ; Enteric nervous system ; Immunohistochemistry ; Noradrenaline ; Somatostatin ; Substance P
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    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 306 (1979), S. 195-201 
    ISSN: 1432-1912
    Keywords: Substance P ; Guinea-pig ileum ; Densensitization ; Peptidergic nerves ; Immunofluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The desensitization of receptors for substance P in the longitudinal muscle of the guinea-pig ileum has been studied. Receptors for substance P in the muscle became desensitized in the presence of relatively large concentrations of synthetic substance P; a desensitizing concentration of substance P of 7.5×10−9 M shifted the concentration-response curve for substance P about 20-fold to the right, while a desensitizing concentration of 7.5×10−8 M shifted the curve about 300-fold to the right. This desensitization appeared specific; concentration-response curves for carbachol, DMPP, 5-HT and bradykinin were not significantly affected by substance P, 7.5×10−8 M. Furthermore, substance P in concentrations up to 7.5×10−8 M did not modify transmission from either cholinergic nerves or enteric inhibitory nerves when these were stimulated electrically. However, hyoscine-resistant contractions produced by stimulation of nerves in the ileum at 10 Hz were abolished by exposure to concentrations of substance P of 7.5×10−9 M or greater, suggesting that these nerves release a substance similar to or identical with substance P. DMPP evoked small hyoscine-resistant contractions of the ileum. These contractions were also antagonised by desensitization of receptors for substance P. Immunohistochemical studies showed substance P-like immunoreactivity in nerve terminals of both the myenteric and submucous plexuses.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 307 (1979), S. 57-63 
    ISSN: 1432-1912
    Keywords: Substance P ; Intestine ; Autonomic nervous system ; Peptidergic nerves
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Acid extracts from both normal and extrinsically denervated ileum contained a compound which was indistinguishable from synthetic substance P; this compound was assayed by examining its contractile effect on the longitudinal muscle of segments of ileum in which receptors for acetylcholine and histamine were blocked. Contractions caused by the compound were markedly and selectively antagonized when the ileum was made insensitive to the action of substance P. The activities in the extract and of synthetic substance P were both destroyed by chymotrypsin but were not affected by trypsin or carboxypeptidase B. The concentrations of substance P-like material in normal and extrinsically denervated segments were not significantly different, being equivalent to 0.48 μg of substance P per g of external muscle plus myenteric plexus. A compound with substance P-like activity was liberated by stimulation of intramural nerves, either electrically or by dimethylphenylpiperazinium, in both normal and extrinsically denervated segments of ileum. The release of this compound was prevented by tetrodotoxin and its action on the muscle was blocked when the ileum was made insensitive to the action of substance P. Experiments with transmural stimulation showed that excitatory nerve pathways involving substance P neurons extend for less than 4 cm along the intestine.
    Type of Medium: Electronic Resource
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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    ISSN: 1432-0878
    Keywords: Substance P ; Calcitonin gene-related peptide ; Dynorphin ; Cholecystokinin ; Neuropeptide coexistence ; Sensory neurons ; Immunohistochemistry ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The co-existence of immunoreactivities to substance P (SP), calcitonin gene-related peptide (CGRP), cholecystokinin (CCK) and dynorphin (DYN) in neurons of the dorsal root ganglion (DRG) of guinea-pigs has been investigated with a double-labelling immunofluorescence procedure. Four main populations of neurons could be identified that contained different combinations of these peptides and had distinctive peripheral projections: (1) Neurons that contained immunoreactivity to SP, CGRP, CCK and DYN were distributed mainly to the skin. (2) Neurons with immunoreactivity to SP, CGPR and CCK, but not DYN, were distributed mainly to the small blood vessels of skeletal muscles. (3) Neurons with immunoreactivity to SP, CGRP and DYN, but not CCK, were distributed mainly to pelvic viscera and airways. (4) Neurons containing immunoreactivity to SP and CGRP, but not CCK and DYN, were distributed mainly to the heart, systemic blood vessels, blood vessels of the abdominal viscera, airways and sympathetic ganglia. Other small populations of DRG neurons containing SP, CGRP or CCK alone also were detected. Perikarya containing these combinations of neuropeptides were not found in autonomic ganglia. The peripheral axons of neurons containing immunoreactivity to at least SP and CGRP were damaged by chronic treatment with capsaicin. However, some sensory neurons containing CCK alone were not affected morphologically by capsaicin. These results clearly show that individual DRG neurons can contain many different neuropeptides. Furthermore, the combination of neuropeptides found in any particular neuron is related to its peripheral projection.
    Type of Medium: Electronic Resource
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