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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 527 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 117-142 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract The enteric nervous system exerts local control over mixing and propulsive movements in the small intestine. When digestion is in progress, intrinsic primary afferent neurons (IPANs) are activated by the contents of the intestine. The IPANs that have been physiologically characterized are in the intrinsic myenteric ganglia. They are numerous, about 650/mm length of small intestine in the guinea pig, and communicate with each other through slow excitatory transmission to form self-reinforcing assemblies. High proportions of these neurons respond to chemicals in the lumen or to tension in the muscle; physiological stimuli activate assemblies of hundreds or thousands of IPANs. The IPANs make direct connections with muscle motor neurons and with ascending and descending interneurons. The circular muscle contracts as an annulus, about 2-3 mm in minimum oral-to-anal extent in the guinea pig small intestine. The smooth muscle cells form an electrical syncytium that is innervated by about 300 excitatory and 400 inhibitory motor neurons per mm length. The intrinsic nerve circuits that control mixing and propulsion in the small intestine are now known, but it remains to be determined how they are programmed to generate the motility patterns that are observed.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 29 (1989), S. 289-306 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 4 (1977), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The amounts by which various weights distended isolated segments from the distal colons of guinea-pigs were measured.2. Tetrodotoxin substantially reduced the distensibility of the intestine, but bretylium, guanethidine, hyoscine and methysergide had no significant effect.3. It is concluded that a local reflex involving enteric inhibitory nerves causes an accommodation of the intestine to stretch.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 8 (1981), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Concentrations of noradrenaline, adrenaline and dopamine were measured in the submucosa and myenteric plexus of innervated and extrinsically denervated guinea-pig ileum using a sensitive radioisotope enzymatic assay for catecholamines.2. Subcellular fractionation studies indicated that the microsomal fraction obtained from both layers of the normal ileum was greatly enriched with noradrenaline compared to the total homogenate. Low levels of adrenaline and dopamine were also detected in both layers of the ileum.3. After extrinsic denervation or pretreatment with reserpine, noradrenaline was reduced to less than 3% and could no longer be visualized histochemically. Small proportions of the adrenaline and dopamine also disappeared after extrinsic denervation.4. The residual amounts of noradrenaline, adrenaline and dopamine present after extrinsic denervation were not sensitive to reserpine and were not concentrated in microsomal fractions suggesting that these amines are not stored as neurotransmitters in intrinsic neurons of the intestine.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 19 (2004), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A subset of myenteric neurons in the intestine (AH neurons) generate prolonged (〉5 s) post-spike afterhyperpolarizations (slow AHPs) that are insensitive to apamin and tetraethylammonium. Generation of slow AHPs depends critically on Ca2+ entry and intracellular release of Ca2+ from stores, which then leads to the activation of a K+ conductance that underlies the slow AHP (gsAHP). Slow AHPs are inhibited by stimulation of the cAMP/protein kinase A (PKA) pathway, suggesting that phosphorylation of the K+-channels that mediate the gsAHP (KsAHP-channels) is responsible for suppression of slow AHPs and possibly for the repolarization phase of slow AHPs. In the present study, we investigated the possibility that the rising phase of the slow AHP is mediated by dephosphorylation of KsAHP-channels by calcineurin (CaN), a Ca2+-calmodulin-dependent protein phosphatase, leading to an increase in gsAHP and activation of the associated current IsAHP. Slow AHPs and IsAHP were recorded using conventional recording techniques, and we tested the actions of two inhibitors of CaN, FK506 and cyclosporin A, and also the effect of the CaN autoinhibitory peptide applied intracellularly, on these events. We report here that all three treatments inhibited the slow AHP and IsAHP (〉70%) without significantly affecting the ability of neurons to fire action potentials. In addition, the slow AHP and IsAHP were suppressed by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. Our results indicate that activation of the gsAHP that underlies the post-depolarization slow AHPs in AH neurons is mediated by the actions CaN and non-Ca2+-dependent phosphatases.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 547 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 8
    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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  • 9
    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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  • 10
    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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