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  • 1
    Electronic Resource
    Electronic Resource
    Characterization of 5-HT receptors mediating contraction and relaxation of the longitudinal muscle of guinea-pig distal colon in vitro (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 455-462 
    Details
    ISSN: 1432-1912
    Keywords: 5-HT receptors ; Guinea-pig colon ; Longitudinal muscle ; Tachykinins ; Enteric neurons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A range of agonists and antagonists were used to characterize the receptors through which 5-hydroxytryptamine (5-HT) contracts and relaxes the longitudinal muscle of segments of guinea-pig distal colon, in vitro. 5-HT contracted the longitudinal muscle over the concentration range 10−9 to 10−4 mol/l. The 5-HT3 receptor agonist, 2-methyl-5-HT, produced concentration dependent contractions over the range 10−6 to 10−4 mol/l. 5-methoxytryptamine, an agonist at 5-HT4 receptors, caused contractions over a concentration range of 10−8 to 10−4 mol/l. The 5-HT4 antagonist, SDZ 205-557 (5 × 10−7 mol/l) substantially suppressed the responses to low concentrations of 5-HT and to 5-methoxytryptamine, but had no effect on the responses to higher concentrations of 5-HT. In contrast, the 5-HT3 antagonist, granisetron (10−6 mol/l), blocked the effect of 2-methyl-5-HT and substantially depressed responses to high concentrations of 5-HT, but had no effect on lower concentrations of 5-HT. Granisetron produced a small reduction in the response to 5-methoxytryptamine. Tetrodotoxin (TTX) (3 × 10−7 mol/l) almost abolished the response to 5-methoxytryptamine and markedly suppressed the response to 2-methyl-5-HT, but the responses to 5-HT were only partially reduced. The 5-HT, antagonist, methiothepin 10−6 mol/l. depressed the response to 5-HT 10−7 to 10−4 mol/l. and blocked its TTX insensitive component. The 5-HT2 antagonist, ketanserin, in concentrations up to 10−5 mol/l, had no effect on the contractions evoked by 5-HT. The response to 5-HT was substantially depressed by hyoscine (3 × 10−6 mol/l. The tachykinin antagonist, spantide 10−5 mol/l. depressed the response to 5-HT but to a lesser extent than hyoscine. Spantide and hyoscine combined completely blocked the contractile responses to 5-HT Responses to 2-methyl-5-HT were partially suppressed by hyoscine (3 x 10−6 mol/l. and spantide (10−5 mol/l) and completely blocked when both byoscine and spantide were present. Contractions evoked by 5-methoxytryptamine were partially blocked by hyoscine (3 × 10−6 mol/l) and were unaffected by spantide (10−5 mol/l), but a combination of hyoscine and spantide completely blocked such responses. When the excitatory transmission was blocked with hyoscine (3 × 10−6 mol/l) and spantide 10−5 mol/l) and the tone of the muscle raised, an inhibitory response to 5-HT was revealed that had a threshold concentration between 10−7 mol/l) and 3 × 10−7 mol/l, and a maximum effect at 10−4 mol/l. It was blocked by TTX (3 × 10−7 mol/l) and granisetron 10−6 mol/l. while N-nitro-l-arginine (NOLA) (10−4 mol/l) and SDZ 205-557 (5 × 10−7 mol/l) had no effect. Apamin A 10−6 mol/l. partially suppressed this response. It is concluded that 5-HT3, 5-HT4 and 5-HT1-like receptors mediate contraction of the longitudinal muscle of the distal colon. The 5-HT3 and 5-HT4 receptors are located on the excitatory motor neurons innervating the longitudinal muscle and the 5-HT1-like receptor is located on the muscle. 5-HT3 receptors are also found on inhibitory neurons to the muscle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169133
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  • 2
    Electronic Resource
    Electronic Resource
    The distributions and coexistence of peptides in nerve fibres of large bowel affected by Hirschsprung's disease (1991)
    Springer
    Pediatric surgery international 6 (1991), S. 322-332 
    Details
    ISSN: 1437-9813
    Keywords: Neuropeptides ; Coexistence ; Hirschsprung's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distributions of nerve fibres immunoreactive for the peptides calcitonin gene-related peptide (CGRP), enkephalin (ENK), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP), and vasoactive intestinal peptide (VIP) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) were studied in healthy colon and samples of ganglionic and aganglionic colon from cases of proven Hirschsprung's disease. Studies of coexistence of reactivities in nerve fibres were performed to predict the possible origins of fibres that are found in the aganglionic bowel, e. g., from sensory or sympathetic ganglia. The muscularis externa of the ganglionic colon contained many nerve fibres immunoreactive for ENK, SP, and VIP, fewer for NPY, and only rare fibres reactive for CGRP, SOM, or TH. In ganglionic colon reactivities for SP and ENK coexisted in nerve fibres in the muscularis externa but in aganglionic colon no ENK immunoreactivity was found and most SP fibres were double-labelled with CGRP reactivity, indicating their probable sensory nature. Abnormally increased numbers of somatostatin-reactive fibres and noradrenergic fibres (marked by TH) were noted in the external muscle, but no coexistence was seen between these reactivities and only a small proportion of the noradrenergic fibres in the muscle showed NPY reactivity although almost all around blood vessels did. Many fibres in the diseased segment had coexistence of NPY and VIP reactivities; these may arise from more orally located intrinsic cell bodies or from pelvic parasympathetic ganglia. In the mucosa of aganglionic colon there was a striking lack of SP-reactive fibres while other fibre types were often normal in number. It is concluded that nerve fibres from sensory ganglia, sympathetic ganglia, nerve cells located more oral in the ganglionated part, and possibly from pelvic parasympathetic ganglia invade the aganglionic bowel in Hirschsprung's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00178648
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  • 3
    Electronic Resource
    Electronic Resource
    Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea-pig intestine (1992)
    Springer
    Histochemistry and cell biology 97 (1992), S. 375-378 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Neuronal nitric oxide synthase (NOS), an enzyme capable of synthesizing nitric oxide, appears to be identical to neuronal NADPH diaphorase. The correlation was examined between NOS immunoreactivity and NADPH diaphorase staining in neurons of the ileum and colon of the guinea-pig. There was a one-to-one correlation between NOS immunoreactivity and NADPH diaphorase staining in all neurons examined; even the relative staining intensities obtained were similar with each technique. To determine whether pharmacological methods could be employed to demonstrate that NADPH diaphorase staining was due to the presence of NOS, tissue was pre-treated with NG-nitro-l-arginine, a NOS inhibitor, or l-arginine, a natural substrate of NOS. In these experiments on unfixed tissue, it was necessary to use dimethyl thiazolyl tetrazolium instead of nitroblue tetrazolium as the substrate for the NADPH diaphorase histochemical reaction. Neither treatment caused a significant decrease in the level of NADPH diaphorase staining, implying that arginine and NADPH interact at different sites on the enzyme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00270041
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  • 4
    Electronic Resource
    Electronic Resource
    Charybdotoxin and iberiotoxin but not apamin abolish the slow after-hyperpolarization in myenteric plexus neurons (1994)
    Springer
    Pflügers Archiv 428 (1994), S. 300-306 
    Details
    ISSN: 1432-2013
    Keywords: Potassium channels ; Enteric nervous system ; After-hyperpolarization ; Toxins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Myenteric neurons of guinea-pig ileum were studied with intracellular microelectrodes. The specific toxins charybdotoxin, iberiotoxin and apamin were used to characterize the prolonged after-hyperpolarizations of AH neurons in this preparation. Charybdotoxin and iberiotoxin blocked prolonged after-hyperpolarizations in 23 of 24 AH neurons, but apamin had no effect on 5 of 5 AH neurons. Abolition of the after-hyperpolarizations was accompanied by depolarization and increases in input resistances of those AH neurons affected, but the shapes of action potentials were unchanged. The excitability of the AH neurons was enhanced as shown by an increase in the number of action potentials evoked by a 500-ms depolarizing current pulse or by a train of 15 ms depolarizing current pulses (10Hz). The other class of myenteric neurons, S neurons, was also investigated. The 19 S neurons studied fired action potentials only at the start of a 500 ms depolarization, but the toxins had no effect on this behaviour or on their other properties. Intracellular injection of Neurobiotin into the neurons studied and subsequent immunohistochemical staining to localise the calcium-binding protein, calretinin, indicated that all major classes of S neurons were included in the sample. Thus, the prolonged after-hyperpolarizations in AH neurons may be due to opening of a large-conductance (BK) calcium-dependent potassium channel, but similar channels play little or no role in regulation of the excitability of S neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00724511
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  • 5
    Electronic Resource
    Electronic Resource
    Nitric oxide synthase in the enteric nervous system of the guinea-pig: a quantitative description (1994)
    Springer
    Cell & tissue research 277 (1994), S. 139-149 
    Details
    ISSN: 1432-0878
    Keywords: NADPH diaphorase ; Immunohistochemistry ; Gastrointestinal tract ; Nitric oxide ; Histochemistry ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution and abundance of nitric oxide synthase (NOS)-containing neurons and their terminals in the gastrointestinal tract of the guinea-pig were examined in detail using NADPH diaphorase histochemistry and NOS immunohistochemistry. NOS-containing cell bodies were found in the myenteric plexus throughout the gastrointestinal tract and in the submucous plexus of the stomach, colon and rectum. NOS-containing neurons comprised between 12% (in the duodenum) and 54% (in the esophagus) of total myenteric neurons. In the ileum, NOS neurons represented 19% of total myenteric neurons. Most of the NOS neurons throughout the gastrointestinal tract possessed lamellar dendrites and a single axon. NOS-containing terminals were abundant in the circular muscle, including that of the sphincters, but were rare in the longitudinal muscle, except for the taeniae of the caecum. The muscularis mucosae of the esophagus, stomach, colon and rectum received a medium to dense innervation by NOS terminals. Within myenteric ganglia, NOS-containing terminals were extremely sparse in the esophagus, stomach and duodenum, common in the ileum and distal colon and extremely dense in the proximal colon and rectum. The submucous plexus in the ileum and large intestine contained a sparse plexus of NOS-containing terminals. NOS terminals were not observed in the mucosa of any region. We conclude that throughout the gastrointestinal tract of the guinea-pig, NOS neurons are inhibitory motor neurons to the circular muscle; in the ileum and large intestine, NOS neurons may also function as interneurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00303090
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  • 6
    Electronic Resource
    Electronic Resource
    Calbindin neurons of the guinea-pig small intestine: quantitative analysis of their numbers and projections (1990)
    Springer
    Cell & tissue research 260 (1990), S. 261-272 
    Details
    ISSN: 1432-0878
    Keywords: Calbindin ; Enteric nervous system ; Intestine, small ; Sensory neurons ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of nerve cells with immunoreactivity for the calcium-binding protein, calbindin, has been studied in the small intestine of the guinea-pig, and the projections of these neurons have been analysed by tracing their processes and by examining the consequences of nerve lesions. The immunoreactive neurons were numerous in the myenteric ganglia; there were 3500±100 reactive nerve cells per cm2 of undistended intestine, which is 30% of all nerve cells. In contrast, reactive nerve cells were extremely rare in submucous ganglia. The myenteric nerve cells were oval in outline and gave rise to several long processes; this morphology corresponds to Dogiel's type-II classification. Processes from the cell bodies were traced through the circular muscle in perforating nerve fibre bundles. Other processes ran circumferentially in the myenteric plexus. Removal of the myenteric plexus, allowing time for subsequent fibre degeneration, showed that reactive nerve fibres in the submucous ganglia and mucosa came from the myenteric cell bodies. Operations to sever longitudinal or circumferential pathways in the myenteric plexus indicated that most reactive nerve terminals in myenteric ganglia arise from myenteric cell bodies whose processes run circumferentially for 1.5 mm, on average. It is deduced that the calbindin-reactive neurons are multipolar sensory neurons, with the sensitive processes in the mucosa and with other processes innervating neurons of the myenteric plexus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318629
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  • 7
    Electronic Resource
    Electronic Resource
    Distribution of enteric nerve cells projecting to the superior and inferior mesenteric ganglia of the guinea-pig (1993)
    Springer
    Cell & tissue research 271 (1993), S. 333-339 
    Details
    ISSN: 1432-0878
    Keywords: Enteric nervous system ; Prevertebral ganglia ; Retrograde tracing ; Calbindin ; Vasoactive intestinal peptide (VIP) ; Intestine ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Retrograde tracing, using Fast Blue dye, was employed to determine the distribution of enteric nerve cells that project to the superior mesenteric and inferior mesenteric ganglia of the guinea-pig. Retrogradely labelled neurons were found in the myenteric but not submucous ganglia. When the superior mesenteric ganglion was injected, labelled neurons were found in low frequencies (less than 5 nerve cell bodies/cm2) in the duodenum, jejunum, ileum, caecum and proximal colon. The distal colon was analysed in five segments of equal length (1–5; oral to anal). Segment 1 had about 4 labelled nerve cells/cm2, whereas segments 2 to 5 displayed an average of about 25 nerve cells/cm2. The rectum contained about 36 labelled neurons/cm2. After injection of the inferior mesenteric ganglia with Fast Blue, no labelled neurons were found in the duodenum, jejunum, ileum or caecum. No labelled cells were observed in the gallbladder. A small number of labelled cells occurred in the proximal colon and in segment 1 of the distal colon. The frequency of labelled cells increased markedly in the more anal regions of the distal colon, and reached a peak in the rectum (138 cells/cm2). Both nerve lesions and immersion of the cut nerve in Fast Blue solution showed that the superior mesenteric nerve carries the axons of neurons located in the middle distal colon to the superior mesenteric ganglion. Almost half of the neurons in the rectum that project to the inferior mesenteric ganglia do so via the hypogastric nerves. Of neurons that projected to the inferior or superior mesenteric ganglia from the colon or rectum, similar proportions (about 75–80%) showed immunoreactivity for calbindin or VIP. For each of the prevertebral ganglia (coeliac, superior mesenteric and inferior mesenteric) the great majority of peripheral inputs arise from the large intestine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318620
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  • 8
    Electronic Resource
    Electronic Resource
    Light- and electron-microscopic immunochemical analysis of nerve fibre types innervating the taenia of the guinea-pig caecum (1992)
    Springer
    Cell & tissue research 270 (1992), S. 125-137 
    Details
    ISSN: 1432-0878
    Keywords: Enteric nervous system ; Caecum ; Neurochemistry ; Neuropeptides ; Nitric oxide synthase ; Chemical coding ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present work was undertaken to determine by immunocytochemical methods which of the putative enteric neurotransmitters are contained in axons supplying the guinea-pig taenia coli and what proportion of axons is accounted for by the presence of these substances. Numerous fibres displayed immunoreactivity for dynorphin (DYN), enkephalin (ENK), γ-aminobutyric acid (GABA), nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP), but, in contrast to other gut regions, fibres showing immunoreactivity for gastrin-releasing peptide, galanin and neuropeptide Y were rare in the taenia. Fibres reactive for calbindin, calcitonin gene-related peptide, cholecystokinin, 5-hydroxytryptamine and somatostatin were also rare. Tyrosine hydroxylase-like immunoreactivity (TH-LI) was present in numerous fibres that disappeared after extrinsic denervation, a procedure that did not detectably affect any of the other major groups of fibres. Simultaneous staining of extrinsically denervated preparations revealed that SP-LI and VIP-LI were located in separate fibres, and ultrastructural studies showed these to be 58% and 33% of intrinsic fibres supplying the muscle. Immunoreactivity for the general marker, neuron-specific enolase, was located in 95–98% of axons. ENK-LI and DYN-LI were in the same axons, and similar proportions of the fibres with either SP-LI or VIP-LI, about 85%, contained immunoreactivity for ENK and DYN. All VIP-LI fibres, but no SP-LI fibres, were reactive for NOS. The results imply that the taenia of the guinea-pig caecum is innervated by two major groups of enteric neurons: (i) excitatory neurons that contain ACh, SP, other tachykinins, and, in most cases, DYN-LI and ENK-LI; and (ii) inhibitory neurons that contain NOS-LI, VIP-LI, in most cases, the two opioids and, quite probably, ATP as a transmitter. GABA-LI is contained in a smaller population of intrinsic axons. Even though the taenia represents one of the simplest tissues for examining transmission from enteric neurons to intestinal muscle, it shares some of the complexity of other regions, in that four major axon types supply the muscle and both the enteric excitatory and enteric inhibitory neurons contain multiple transmitters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00381887
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  • 9
    Electronic Resource
    Electronic Resource
    Evidence that myenteric neurons of the gastric corpus project to both the mucosa and the external muscle: myectomy operations on the canine stomach (1991)
    Springer
    Cell & tissue research 266 (1991), S. 475-481 
    Details
    ISSN: 1432-0878
    Keywords: Enteric nervous system ; Stomach ; Vasoactive intestinal peptide ; Galanin ; Gastrin-releasing peptide ; Substance P-Dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of nerve cell bodies and fibres in the canine stomach was investigated using antibodies to the general neuronal marker, neuron-specific enolase. Prominent ganglia containing many reactive nerve cells were found in the myenteric plexus of the gastric corpus and antrum. Nerve cells were absent from the submucosa of the corpus and were extremely rare in the antrum. Renoval of areas of longitudinal muscle and myenteric plexus from the corpus (myectomy), with 7 days allowed for axon degeneration, resulted in the loss of fibres reactive for galanin, gastrin-releasing peptide, substance P and vasoactive intestinal peptide from both the circular muscle and mucosa in the area covered by the lesion. Combined vagotomy and sympathetic denervation did not significantly affect these fibres, but did cause fibres reactive for calcitonin gene-related peptide to degenerate. It is concluded that the myenteric plexus of the gastric corpus, like the myenteric plexus of the small intestine and colon, is the source of nerve fibres innervating the circular muscle, but, in contrast to other regions of the gastrointestinal tract, myenteric ganglia, not submucous ganglia, are the major, or sole, source of the intrinsic innervation of the mucosa.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318588
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  • 10
    Electronic Resource
    Electronic Resource
    Calretinin-immunoreactive neurons and their projections in the guinea-pig colon (1994)
    Springer
    Cell & tissue research 276 (1994), S. 359-365 
    Details
    ISSN: 1432-0878
    Keywords: Calretinin ; Enteric nervous system ; Calcium-binding protein ; Colon ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution of nerve cells and fibres with immunoreactivity for the calcium-binding protein, calretinin, was studied in the distal colon of the guinea-pig. The projections of the neurons were determined by examining the consequences of lesioning the myenteric plexus. Calretinin-immunoreactive neurons comprised 17% of myenteric nerve cells and 6% of submucous nerve cells. Numerous calretinin-immunoreactive nerve fibres were located in the longitudinal and circular muscle, and within the ganglia of the myenteric and submucous plexuses. Occasional fibres were found in the muscularis mucosae, but they were very rare in the lamina propria of the mucosa. Lesion studies revealed that myenteric neurons innervated the underlying circular muscle and provided both ascending and descending processes that gave rise to varicose branches in myenteric ganglia. Calretinin-immunoreactive fibres also projected to the tertiary component of the myenteric plexus, and are therefore likely to be motor neurons to the longitudinal muscle. Varicose fibres that supplied the submucous ganglia appear to arise from submucous nerve cells. Arterioles of the submucous plexus were sparsely innervated by calretinin-immunoreactive fibres. The submucous plexus was the principal source of immunoreactive nerve fibres in the muscularis mucosae. This work shows that calretinin-IR reveals different neuronal populations in the large intestine to those previously reported in the small intestine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00306121
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