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  • 1
    Electronic Resource
    Electronic Resource
    Effects of noradrenaline and somatostatin on basal and stimulated mucosal ion transport in the guinea-pig small intestine (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 333 (1986), S. 393-399 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00500015
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  • 2
    Electronic Resource
    Electronic Resource
    Evidence that axons containing substance P in the guinea-pig ileum are of intrinsic origin (1979)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 307 (1979), S. 57-63 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00506552
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  • 3
    Electronic Resource
    Electronic Resource
    Substance P enteric neurons mediate non-colinergic transmission to the circular muscle of the guinea-pig intestine (1985)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 328 (1985), S. 446-453 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00692914
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  • 4
    Electronic Resource
    Electronic Resource
    Different substance P receptors are found on mucosal epithelial cells and submucous neurons of the guinea-pig small intestine (1985)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 329 (1985), S. 382-387 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00496372
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  • 5
    Electronic Resource
    Electronic Resource
    Evidence for the release of endogenous substance P from intestinal nerves (1979)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 195-201 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00507103
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  • 6
    Electronic Resource
    Electronic Resource
    Innervation of the large arteries and heart of the toad (Bufo marinus) by adrenergic and peptide-containing neurons (1986)
    Springer
    Cell & tissue research 243 (1986), S. 171-184 
    Details
    ISSN: 1432-0878
    Keywords: Perivascular nerves ; Cardiac innervation ; Neuropeptides ; Neuropeptide Y ; Substance P ; Adrenergic nerves ; Amphibia, Anura (Bufo marinus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The innervation of the major arteries and heart of the toad (Bufo marinus) was examined by use of glyoxylic acid-induced catecholamine fluorescence and peptide immunohistochemistry. All arteries possessed a moderate to dense plexus of adrenergic axons, which also showed neuropeptide Y-like immunoreactivity (NPY-LI). Some adrenergic axons in the intracardiac vagal trunks showed NPY-LI, but the varicose adrenergic axons innervating the cardiac muscle of the atria and ventricle, and the coronary blood vessels did not display NPY-LI. About half of the nerve cell bodies in the anterior sympathetic chain ganglia with dopamine-β-hydroxylase-LI (DBH-LI) also contained NPY-LI. The nerve cell bodies with DBH-LI alone were generally larger (median diameter 30 μm) than those with both DBH-LI and NPY-LI (median diameter 20 μm). Some cell bodies showing DBH-LI alone were surrounded by boutons with NPY-LI but not DBH-LI. Axons that displayed simultaneously both substance P-LI (SP-LI) and calcitonin gene-related peptide-LI (CGRP-LI) also formed a plexus around all arteries studied, being particularly dense around the mesenteric and pulmonary arteries. These axons are most likely sensory since SP-LI was reduced by capsaicin treatment, and nerve cell bodies with both SP-LI and CGRP-LI were found in dorsal root ganglia and the vagal ganglion. A dense plexus of axons showing somatostatin-LI was located around the pulmonary artery and its main intrapulmonary branches. A few nerves with vasoactive intestinal polypeptide-LI were found around the dorsal aorta and pulmonary artery. No perivascular nerves with enkephalin-LI were observed. Reversed-phase, high-pressure liquid chromatography of acid extracts of the large arteries showed that the major peaks of NPY-LI and SP-LI coeluted with porcine NPY (1–36) and synthetic SP (1–11), respectively. Thus, the location and structure of these peptides in perivascular nerves has been highly conserved during vertebrate evolution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00221866
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  • 7
    Electronic Resource
    Electronic Resource
    Calretinin immunoreactivity of motor neurons in the guinea-pig distal colon and taenia coli (1996)
    Springer
    Cell & tissue research 284 (1996), S. 367-372 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Calretinin ; Calcium-binding protein ; Enteric nervous system ; Distal colon ; Taenia coli ; Vasoactive intestinal peptide (VIP) ; Substance P ; γ-Aminobutyric acid (GABA) ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Calretinin is a calcium-binding protein which occurs in neurons and endocrine cells, including neurons throughout the gastrointestinal tract. Calretinin-immunoreactive (IR) neurons innervate the circular muscle in the guinea-pig distal colon and have descending as well as ascending projections. This suggests that calretinin-IR is in motor neurons, but whether it might be in excitatory or inhibitory motor neurons or both was previously undetermined. The presence of calretinin-IR in neurons innervating the taenia coli has not been previously reported. Numerous fibres in the circular muscle of the distal colon and in the taenia coli displayed immunoreactivity for calretinin. Tachykinin (TK), vasoactive intestinal peptide (VIP), calretinin, and γ-aminobutyric acid (GABA) immunoreactivity was also in fibres innervating these targets. The abundances of these fibres was estimated to be TK〉VIP〉calretinin〉GABA. Double label immunohistochemistry revealed the presence in both tissues of populations of calretinin-IR fibres which were also TK-IR, and fibres with calretinin and GABA-IR in the colon, but calretinin-IR fibres were never VIP-IR. TK- and VIP-IR were in separate populations of nerve fibres as were GABA- and TK-IR. It is concluded that calretinin-IR does not provide a definitive labelling of a physiologically known subgroup of motor neurons, either in the distal colon or in the taenia coli, but that calretinin is most likely to be in excitatory motor neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050597
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  • 8
    Electronic Resource
    Electronic Resource
    Identification of the populations of enteric neurons that have NK1 tachykinin receptors in the guinea-pig small intestine (1998)
    Springer
    Cell & tissue research 294 (1998), S. 27-33 
    Details
    ISSN: 1432-0878
    Keywords: Key words Enteric nervous system ; Tachykinins ; Receptor localisation ; Substance P ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Simultaneous immunofluorescence labelling was used to investigate the patterns of colocalisation of the NK1 tachykinin receptor with other neuronal markers, and hence determine the functional classes of neuron that bear the NK1 receptor in the guinea-pig ileum. In the myenteric plexus, 85% of NK1 receptor-immunoreactive (NK1r-IR) nerve cells had nitric oxide synthase (NOS) immunoreactivity and the remaining 15% were immunoreactive for choline acetyltransferase (ChAT). Of the latter group, about 50% were immunoreactive for both neuropeptide Y (NPY) and somatostatin (SOM), and had the morphologies of secretomotor neurons. Many of the remaining ChAT neurons were immunoreactive for calbindin or tachykinins (TK), but not both. These calbindin immunoreactive neurons had Dogiel type II morphology. No NK1r-IR nerve cells in the myenteric plexus had serotonin or calretinin immunoreactivity. In the submucosal ganglia, 84% of NK1r-IR nerve cells had neuropeptide Y immunoreactivity and 16% were immunoreactive for TK. It is concluded that NK1r-IR occurs in five classes of neuron; namely, in the majority of NOS-immunoreactive inhibitory motor neurons, in ChAT/TK-immunoreactive excitatory neurons to the circular muscle, in all ChAT/NPY/SOM-immunoreactive secretomotor neurons, in a small proportion of ChAT/calbindin myenteric neurons, and in about 50% of ChAT/TK submucosal neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051153
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  • 9
    Electronic Resource
    Electronic Resource
    Quantitative analysis of inputs to somatostatin-immunoreactive descending interneurons in the myenteric plexus of the guinea-pig small intestine (1998)
    Springer
    Cell & tissue research 294 (1998), S. 219-226 
    Details
    ISSN: 1432-0878
    Keywords: Key words Enteric nervous system ; Somatostatin ; Immunocytochemistry ; Intestinal motility ; Synaptic connections ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Somatostatin immunoreactivity occurs in a specific subgroup of cholinergic descending interneurons in the myenteric plexus of the guinea-pig small intestine. In the present work, we made light- and electron-microscopic investigations of chemically defined inputs to these neurons, in order that the origins of the connections of other neurons with them could be deduced. Somatostatin-immunoreactive synapses and close contacts were found on the cell bodies and filamentous processes of somatostatin neurons; these were 84% of all inputs. It is thus confirmed that this class of interneuron forms chains that project anally. Descending interneurons with immunoreactivity for nitric oxide synthase provided 14% of inputs to somatostatin-immunoreactive descending interneurons. An antiserum against a calcium-binding protein, calbindin, was used as marker for the majority of intrinsic primary afferent neurons, AH/Dogiel type II neurons; this class of neurons provided only 2.5% of the inputs to somatostatin-immunoreactive descending interneurons. We conclude that somatostatin-immunoreactive descending interneurons are involved in the conduction of impulses distally along the full length of the small intestine, but receive only a minor input from calbindin-immunoreactive primary afferent neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051171
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  • 10
    Electronic Resource
    Electronic Resource
    Somatostatin in human enteric nerves (1984)
    Springer
    Cell & tissue research 237 (1984), S. 299-308 
    Details
    ISSN: 1432-0878
    Keywords: Somatostatin ; Somatostatin immunoreactivity ; Somatostatin-containing neurons ; Stomach ; Intestine small ; Intestine, large ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Somatostatin-immunoreactive nerves and endocrine cells were localized by use of immunohistochemistry in human stomach, small and large intestine. The nature of the immunoreactivity in acid extracts of separated layers of intestine was determined with separation by high pressure liquid chromatography followed by detection with radioimmunoassay; authentic somatostatin-14 was found in the external musculature, which contains nerves, and in the submucosa and mucosa, which contain both nerve fibres and endocrine cells. The distribution of somatostatin nerves in the gastric antrum, duodenum, jejunum, ileum, ascending and sigmoid colon, and rectum is described. In the intestine many positive perikarya and fine varicose fibres were seen. Mucosal fibres formed a sub-epithelial plexus and a looser network in the lamina propria; this nerve supply was less dense in the large intestine. Submucous ganglia contained positive perikarya and terminals; many terminals formed pericellular baskets, mainly around non-reactive cells. A small number of nerve fibres were associated with submucosal blood vessels. The innervation of the circular and longitudinal muscle was sparse. Positive nerve terminals were seen in the myenteric plexus, although fewer than in the submucous ganglia; positive perikarya were scarce in myenteric ganglia. Somatostatin-immunoreactive nerves were found in the muscle layers and myenteric plexus of the gastric antrum, but were not detected in the antral mucosa and all layers of the gastric body. The distribution of human enteric somatostatin nerves is compared to that in small laboratory animals, and possible roles for these nerves are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217149
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