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1

Digitale Medien

Branching patterns and projections of enteric neurons containing different putative transmitters

Furness, J.B. ; Costa, M. ; Llewellyn-Smith, I.J.

Amsterdam : Elsevier

Peptides 2 (1981), S. 119-122

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ISSN: 0196-9781

Schlagwort(e): 5-Hydroxytryptamine ; Enteric nervous system ; Immunohistochemistry ; Noradrenaline ; Somatostatin ; Substance P

Quelle: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Thema: Chemie und Pharmazie

Materialart: Digitale Medien

URL: http://linkinghub.elsevier.com/retrieve/pii/0196-9781(81)90022-X

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2

Digitale Medien

Evidence for the release of endogenous substance P from intestinal nerves (1979)

Franco, R. ; Costa, M. ; Furness, J. B.

Springer

Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 195-201

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ISSN: 1432-1912

Schlagwort(e): Substance P ; Guinea-pig ileum ; Densensitization ; Peptidergic nerves ; Immunofluorescence

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: 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.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00507103

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3

Digitale Medien

Substance P enteric neurons mediate non-colinergic transmission to the circular muscle of the guinea-pig intestine (1985)

Costa, M. ; Furness, J. B. ; Pullin, C. O. ; [weitere]

Springer

Naunyn-Schmiedeberg's archives of pharmacology 328 (1985), S. 446-453

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ISSN: 1432-1912

Schlagwort(e): Substance P ; Enteric neurons ; Autonomic nervous system

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: 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.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00692914

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4

Digitale Medien

Different substance P receptors are found on mucosal epithelial cells and submucous neurons of the guinea-pig small intestine (1985)

Keast, J. R. ; Furness, J. B. ; Costa, M.

Springer

Naunyn-Schmiedeberg's archives of pharmacology 329 (1985), S. 382-387

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ISSN: 1432-1912

Schlagwort(e): Substance P ; Enteric neurons ; Mucosal transport

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: 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.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00496372

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5

Digitale Medien

Investigations of nerve populations influencing ion transport that can be stimulated electrically, by serotonin and by a nicotinic agonist (1985)

Keast, J. R. ; Furness, J. B. ; Costa, M.

Springer

Naunyn-Schmiedeberg's archives of pharmacology 331 (1985), S. 260-266

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ISSN: 1432-1912

Schlagwort(e): Enteric neurons ; Serotonin ; Mucosal transport ; Substance P receptor

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: 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.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00634247

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6

Digitale Medien

Evidence that axons containing substance P in the guinea-pig ileum are of intrinsic origin (1979)

Franco, R. ; Costa, M. ; Furness, J. B.

Springer

Naunyn-Schmiedeberg's archives of pharmacology 307 (1979), S. 57-63

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ISSN: 1432-1912

Schlagwort(e): Substance P ; Intestine ; Autonomic nervous system ; Peptidergic nerves

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: 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.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00506552

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7

Digitale Medien

The origins of the adrenergic fibres which innervate the internal anal sphincter, the rectum, and other tissues of the pelvic region in the guinea-pig (1973)

Costa, M. ; Furness, J. B.

Springer

Anatomy and embryology 140 (1973), S. 129-142

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ISSN: 1432-0568

Schlagwort(e): Autonomic nervous system ; Adrenergic nerves ; Pelvic viscera ; Gastrointestinal tract

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: Summary The adrenergic innervation of the pelvic viscera was examined by the fluorescence histochemical technique, applied to tissue from untreated guinea-pigs and from guinea-pigs in which nerve pathways had been interrupted at operation. It was found that adrenergic neurons in the inferior mesenteric ganglia give rise to axons which run in the colonic nerves and end in the myenteric and submucous plexuses and around the arteries of the distal colon. In the rectum, part of the innervation of the myenteric plexus and all of the innervation of the submucous plexus comes from the inferior mesenteric ganglia. The rest of the adrenergic innervation of the myenteric plexus comes from the posterior pelvic ganglia or the sacral sympathetic chains. The innervation of the blood vessels of the rectum is from the posterior pelvic ganglia. Adrenergic nerves run from the sacral sympathetic chains and pass via nerves accompanying the rectal arteries to the internal anal sphincter. Other adrenergic fibres to the internal anal sphincter either arise in, or pass through, the posterior pelvic plexuses. The anal accessory muscle is innervated by adrenergic axons arising in the posterior pelvic plexuses. Adrenergic nerves which run in the pudendal nerves, probably from the sacral sympathetic chains, innervate the erectile tissue of the penis.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00520326

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8

Digitale Medien

The ramifications of adrenergic nerve terminals in the rectum, anal sphincter and anal accessory muscles of the guinea-pig (1973)

Furness, J. B. ; Costa, M.

Springer

Anatomy and embryology 140 (1973), S. 109-128

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ISSN: 1432-0568

Schlagwort(e): Autonomic nervous system ; Gastrointestinal tract ; Adrenergic nerves ; Anal sphincter

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: Summary The anatomy and the adrenergic innervation of the rectum, internal anal sphincter and of accessory structures are described for the guinea-pig. The distribution of adrenergic nerves was examined using the fluorescence histochemical technique applied to both sections and whole mount preparations. The longitudinal and circular muscle of the rectum and the muscularis mucosae are all supplied by adrenergic nerve terminals. The density of the adrenergic innervation of the muscularis externa increases towards the anal sphincter. There is a very dense innervation of the internal anal sphincter, of the anal accessory muscles and of the corrugator ani. Non-fluorescent neurons in the ganglia of the myenteric plexus are supplied by adrenergic terminals. The ganglia become smaller and sparser towards the internal anal sphincter and non-ganglionated nerve strands containing adrenergic axons run from the plexus to the sphincter muscle. Adrenergic fibers innervate two interconnected ganglionated plexuses in the submucosa. Very few adrenergic nerve cells were found in the myenteric plexus and they were not found at all in the submucosa. The extrinsic arteries and veins of the pelvic region are heavily innervated by adrenergic nerves. Within the gut wall the arteries are densely innervated but there is little or no innervation of the veins.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00520721

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9

Digitale Medien

Effects of noradrenaline and somatostatin on basal and stimulated mucosal ion transport in the guinea-pig small intestine (1986)

Keast, J. R. ; Furness, J. B. ; Costa, M.

Springer

Naunyn-Schmiedeberg's archives of pharmacology 333 (1986), S. 393-399

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ISSN: 1432-1912

Schlagwort(e): Enteric neurons ; Mucosal transport ; Noradrenaline ; Somatostatin

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: 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.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00500015

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10

Digitale Medien

The projections of chemically identified nerve fibres in canine ileum (1987)

Daniel, E. E. ; Furness, J. B. ; Costa, M. ; [weitere]

Springer

Cell & tissue research 247 (1987), S. 377-384

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ISSN: 1432-0878

Schlagwort(e): Enkephalin ; Gastrin releasing peptide ; Neuropeptide Y ; Somatostatin ; Substance P ; Vasoactive intestinal peptide ; Enteric nervous system ; Intestine, small ; Dog

Quelle: Springer Online Journal Archives 1860-2000

Thema: Biologie , Medizin

Notizen: 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.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF00218319

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