Effects of extrinsic denervation on innervation with VIP and substance P in circular muscle of rat jejunum

The ultrastructure and immunocytochemistry of the canine distal pyloric muscle loop, the pyloric sphincter, were studied. Cells in this muscle were connected by gap junctions, fewer than in the antrum or corpus. The sphincter had a dense innervation and a sparse population of interstitial cells of Cajal. Most such cells were of the circular muscle type but a few were of the type in the myenteric plexus. Nerves were sometimes associated with interstitial cell profiles, but most nerves were neither close to nor associated with interstitial cells nor close to smooth muscle cells. Nerve profiles were characterized by an unusually high proportion of varicosities with a majority or a high proportion of large granular vesicles. Many of these were shown to contain material immunoreactive for vasoactive intestinal polypeptide (VIP) and some had substance P (SP) immunoreactive material. All were presumed to be peptidergic. VIP was present in a higher concentration in this muscle than in adjacent antral or duodenal circular muscle. Interstitial cells of Cajal made gap junctions to smooth muscle and to one another and might provide myogenic pacemaking activity for this muscle, but there was no evidence of a close or special relationship between nerves with VIP or SP and these cells. The absence of close relationships between nerves and either interstitial cells or smooth muscle cells leaves unanswered questions about the structural basis for previous observations of discrete excitatory responses or pyloric sphincter to single stimuli or nerves up to one per second. In conclusion, the structural observations suggest that this muscle has special neural and myogenic control systems and that interstitial cells may function to control myogenic activity of this muscle but not to mediate neural signals.Key words: vasoactive intestinal polypeptide, interstitial cells of Cajal, neuropeptides, gap junctions, substance P.

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Roles of Substance P Receptors in Human Colon Circular Muscle: Alterations in Diverticular Disease

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.102.034702 ◽

2002 ◽

Vol 302 (2) ◽

pp. 627-635 ◽

Cited By ~ 38

Author(s):

Lu Liu ◽

Fei Shang ◽

Irit Markus ◽

Elizabeth Burcher

Keyword(s):

Substance P ◽

Diverticular Disease ◽

Circular Muscle ◽

Human Colon ◽

Substance P Receptors

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Age-related changes in substance P-immunoreactive nerve structures of the rat recto-anal region

Open Medicine ◽

10.2478/s11536-009-0098-2 ◽

2010 ◽

Vol 5 (3) ◽

pp. 358-364

Author(s):

Nikolai Lazarov ◽

Dimitar Itzev ◽

Kamen Usunoff ◽

Negrin Negrev ◽

Radomir Radomirov

Keyword(s):

Substance P ◽

Anal Sphincter ◽

Internal Anal Sphincter ◽

Circular Muscle ◽

Muscle Layer ◽

Nerve Fibres ◽

Anal Region ◽

Age Related ◽

Old Rats ◽

Age Related Changes

AbstractThe recto-anal region is innervated by extrinsic and intrinsic nerves and a number of neuropeptides including substance P (SP) have been suggested to participate in the regulation of intestinal movements. We examined the age-related changes in the distribution of SP-immunoreactive nerve structures in the distal part of the rat large intestine. Using immunohistochemistry, the presence of SP was studied in fresh tissues from Wistar rats at different ages taken at three sampling sites, the distal rectum, anal canal and internal anal sphincter. In the 15-day old rats the myenteric plexus of the distal rectum and anal canal was well outlined by numerous SP-immunoreactive varicose nerve fibres encircling immunonegative perikarya. In the circular muscle layer, nerve fibres and small nerve bundles ran parallel to the muscle cells, while in the longitudinal muscle layer, only occasional nerve fibres were seen. At the level of the internal anal sphincter, no myenteric ganglia were present. Here, thin varicose fibers ran parallel to the smooth muscle cells. In the 3-month old rats, a larger number of intensely staining SP-immunoreactive nerve fibres were found and in the circular muscle layer, thicker nerve strands were observed. In the 26-month old rats, the density and staining intensity of SP-immunopositive nerve fibres in the myenteric plexus was lower than in the 3-month-old rats. Similar changes in the SP-immunostained fibres in the internal anal sphincter were observed. Degenerative alterations in SP-containing fibres during aging appear to play a role in ano-rectal motility and sphincter control.

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Characterization of the effects of neurokinins on canine antral muscle

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1988.255.6.g779 ◽

1988 ◽

Vol 255 (6) ◽

pp. G779-G786

Author(s):

C. B. Koelbel ◽

E. A. Mayer ◽

G. van Deventer ◽

W. J. Snape ◽

A. Patel

Keyword(s):

Substance P ◽

Mechanical Response ◽

Longitudinal Muscle ◽

Rank Order ◽

Circular Muscle ◽

Neurokinin A ◽

Inotropic Response ◽

Chronotropic Response ◽

Natural Ligand ◽

Dose Dependent

The excitation of longitudinal antral muscle by substance P (SP) involves both a myogenic and a cholinergic effect. To examine if these responses are mediated by different neurokinin receptors, we studied the mechanical response and the release of [3H]acetylcholine from antral muscle strips in response to SP, substance P methylester (SPME), neurokinin A (NKA), neurokinin B (NKB), and several non-mammalian tachykinins. All peptides studied showed a dose-dependent inotropic and chronotropic effect on spontaneous phasic contractions. This ionotropic effect in longitudinal muscle was partially atropine sensitive for SPME, SP, and NKB but not for NKA, whereas neither atropine nor tetrodotoxin had an effect in circular muscle. In longitudinal muscle, all three neurokinins were equipotent. In longitudinal muscle treated with atropine and in circular muscle, the rank order of potency for the inotropic response was NKA greater than NKB greater than SP greater than SPME. For the chronotropic response the rank order was SPME, SP greater than NKA greater than NKB. NKA, NKB, and SP caused a dose-dependent, tetrodotoxin-sensitive increase in [3H]acetylcholine release from strips preincubated with [3H]choline. NKA was significantly more potent to release [3H]acetylcholine than either NKB or SP. The stimulated release was inhibited by [D-Ala2,D-Met5]methionine enkephalinamide and the SP antagonist, spantide. These results are consistent with the hypothesis that NKA is the natural ligand mediating the myogenic inotropic response in both muscle layers and the cholinergic response in longitudinal muscle.

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Downregulation of neutral endopeptidase (EC 3.4.24.11) in the inflamed rat intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.264.4.g735 ◽

1993 ◽

Vol 264 (4) ◽

pp. G735-G743 ◽

Cited By ~ 4

Author(s):

L. Hwang ◽

R. Leichter ◽

A. Okamoto ◽

D. Payan ◽

S. M. Collins ◽

...

Keyword(s):

Substance P ◽

Myenteric Plexus ◽

Longitudinal Muscle ◽

Intestinal Inflammation ◽

Specific Activity ◽

Trichinella Spiralis ◽

Extracellular Fluid ◽

Circular Muscle ◽

Neutral Endopeptidase ◽

Jejunal Mucosa

Intestinal inflammation induced by the nematode Trichinella spiralis is accompanied by increased intestinal concentrations of substance P, a mediator of inflammation and a stimulant of smooth muscle contraction, and by intestinal hypermotility. The expression of neutral endopeptidase (NEP), a cell surface enzyme that degrades substance P in the extracellular fluid, was examined in the inflamed intestine. NEP enzymatic activity, measured by a fluorometric assay, was reduced by 84-fold in jejunal mucosa-circular muscle and by 12-fold in jejunal longitudinal muscle-myenteric plexus within 6 days after infection with T. spiralis. The downregulation was unaffected by treatment with betamethasone and was still observed in athymic animals. NEP protein levels, examined by Western blotting, confirmed the loss of NEP from inflamed tissue. The specific activity for degradation of substance P was reduced by sixfold in jejunal mucosa-circular muscle and by twofold in jejunal longitudinal muscle-myenteric plexus of rats infected with T. spiralis compared with uninfected controls. Thus the downregulation of NEP resulted in reduced substance P degradation, which may contribute to functional abnormalities of the inflamed intestine.

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Ascending enteric reflex: multiple neurotransmitter systems and interactions

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.256.3.g540 ◽

1989 ◽

Vol 256 (3) ◽

pp. G540-G545 ◽

Cited By ~ 6

Author(s):

P. Holzer

Keyword(s):

Small Intestine ◽

Substance P ◽

Guinea Pig ◽

Motor Neurons ◽

Circular Muscle ◽

Neural Pathways ◽

Neurotransmitter Systems ◽

Cholinergic Interneurons

Isolated segments of the guinea pig small intestine were used to examine the transmitter circuitry of the neural pathways subserving the ascending enteric reflex (AER) contraction of the circular muscle. Inflation of an intraluminal balloon provided the distension stimulus for the AER. The ascending contraction was reduced to 5% of its original amplitude by atropine and to 10% by hexamethonium, which indicates that cholinergic interneurons and cholinergic motor neurons constitute the main AER pathway. However, in the continued presence of atropine or hexamethonium for 60 min, the AER recovered to approximately 30% of its original amplitude. The atropine-resistant AER was blocked by hexamethonium and the tachykinin antagonist spantide [( D-Arg1,D-Trp7,9, Leu11]-substance P) suggesting that it involved cholinergic interneurons and tachykinin-utilizing motor neurons. The hexamethonium-resistant AER was abolished by atropine but left unaffected by spantide, suggesting the participation of as yet unidentified interneurons and cholinergic motor neurons. These findings demonstrate that the AER is mediated by multiple neural pathways with different transmitters and that adaptive interactions between these pathways take place after blockade of one of its neurotransmitters systems.

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