Distributions of neuropeptides in the human esophagus

The distributions of nerve cells and fibers with immunoreactivity for the peptides substance P, somatostatin, enkephalin, vasoactive intestinal peptide, gastrin-releasing peptide, and neuropeptide Y and the enzyme tyrosine hydroxylase were examined in 25 samples of human esophagus. These were compared with samples of stomach and intestine. In the smooth muscle of the muscularis externa, the muscularis mucosae, and beneath the epithelium, the most abundant nerve fibers contained vasoactive intestinal peptide and neuropeptide Y, in contrast to the scarcity of substance P, enkephalin, somatostatin, and gastrin-releasing peptide. Gastric and intestinal samples contained dense populations of fibers containing vasoactive intestinal peptide, neuropeptide Y, substance P, and enkephalin in the equivalent layers, but somatostatin- and gastrin-releasing peptide-immunoreactive fibers were scarce. Complete coexistence of vasoactive intestinal peptide and neuropeptide Y in nerve fibers within the muscle layers was demonstrated in the esophagus, but not in gastric and intestinal samples. The myenteric plexus along the length of the esophagus contained cell bodies and fibers reactive for vasoactive intestinal peptide, neuropeptide Y, enkephalin, and substance P. Somatostatin-immunoreactive cell bodies were very rare in the myenteric plexus, no gastrin-releasing peptide-immunoreactive cell bodies were seen, and both somatostatin and gastrin-releasing peptide-immunoreactive fibers were rare. In the upper esophagus, striated muscle bundles did not contain nerve fibers reactive for these peptides but immunoreactive fibers were seen in the muscularis mucosae and subepithelium. It is concluded that the esophagus has a different pattern of innervation by peptide-containing neurons than the stomach and intestines. Esophageal neurons can be classified into separate classes on the basis of their peptide content.     

Abnormalities of peptide-containing nerve fibers in infantile hypertrophic pyloric stenosis

The distributions of nerve cells and fibers with immunoreactivity for the peptides enkephalin, gastrin-releasing peptide, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide were examined in specimens of myenteric plexus and external muscle from the pylorus of 20 infants with hypertrophic pyloric stenosis. These were compared with peptide distributions in pyloric samples from unaffected infants and adults. In the normal pylorus the circular muscle was richly supplied with fibers reactive for enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide. In pyloric stenosis, these immunoreactive fiber bundles were either missing or less than 5% of normal. In contrast, there were reactive cell bodies and nerve fibers in the myenteric plexuses of both normal and affected specimens. In the samples from cases of stenosis, swollen nerve fibers that appeared to be in the process of degeneration were frequently encountered. It is concluded that infantile hypertrophic pyloric stenosis is associated with a loss of peptide immunoreactivity in nerve fibers in the circular muscle, although the same peptides are still revealed in fibers and in nerve cell bodies in the myenteric plexus.     

Distribution and coexistence of peptides in nerve fibers of the external muscle of the human gastrointestinal tract

The nerve fibers that supply the external muscle of the human gastrointestinal tract were examined for their immunoreactivity to the neuropeptides enkephalin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide, for tyrosine hydroxylase (a catecholamine-synthesizing enzyme), and for coexistence between immunoreactivities in nerve fibers. Studies on coexistence revealed that the majority of reactive nerve fibers could be placed in one of two classes: (a) those fibers with reactivity to enkephalin or substance P, or both, and (b) fibers containing one or both of the peptides neuropeptide Y and vasoactive intestinal peptide. Many fibers immunoreactive for vasoactive intestinal peptide or neuropeptide Y, or both, were found throughout the external smooth muscle of the gastrointestinal tract, but neuropeptide Y-reactive fibers were less common in the small and large intestines than in the stomach and esophagus. Fibers immunoreactive for enkephalin or substance P, or both, were sparse in the esophagus, increased in numbers to reach maximal frequency in the pylorus, and maintained a similar frequency in the small and large intestines. Fibers with somatostatin or tyrosine hydroxylase immunoreactivity were rare. In general, sphincter regions were similar to nonsphincter regions in peptide-immunoreactive fiber numbers and types, except that the internal anal sphincter had no enkephalin-immunoreactive fibers and very few substance P-reactive fibers. Moderate numbers of fibers reactive for neuropeptide Y and vasoactive intestinal peptide were found in the internal anal sphincter. It is suggested that enkephalin and substance P are in excitatory fibers and that vasoactive intestinal peptide and neuropeptide Y are in fibers inhibitory to the external muscle.     

Neurochemical coding in the small intestine of patients with Crohn''s disease.

BACKGROUND: There have been conflicting results regarding the effect of Crohn's disease on the neurochemical composition of the enteric nervous system. AIMS: To examine the effect of Crohn's disease on the neurochemical composition of enteric nerve fibres and cell bodies using whole mount preparations of human ileum. METHODS: Whole wall ileum from seven normal subjects and nine patients with Crohn's disease was used to investigate the neurochemical composition of neurones and nerve fibres in the myenteric plexus, circular muscle, and serosa layer of ileum using immunohistochemical techniques. RESULTS: Increased tyrosine hydroxylase, 5-hydroxytryptamine, and neuropeptide Y immunoreactivity was exclusively seen in the myenteric plexus. There was increased neurofilament immunoreactivity in the myenteric plexus and nerve fibres of the circular muscle layer, and thick bundles of immunoreactive nerve fibres in the serosa layer. Increased vasoactive intestinal polypeptide, nitric oxide synthase, and pituitary adenylate cyclase activating peptide immunoreactivity was seen in the myenteric plexus and nerve fibres of the circular muscle layer, and aggregates of inflammatory cells in the serosa layer of the afflicted segment of Crohn's ileum. In addition, there was a chaotic display of nerve fibres containing some of the neuroactive substances with a high frequency of enlarged varicosities in the myenteric ganglia and/or nerve fibres of the circular muscle layer of Crohn's ileum. CONCLUSION: Results show quantitative as well as qualitative changes in the neurochemical composition of enteric nerve fibres and nerve cell bodies of Crohn's ileum. These changes and the presence of nitric oxide synthase and peptides immunoreactive inflammatory cells in the serosa layer suggest that nerve-immune interactions may have a significant role in the process of the inflammatory changes seen in Crohn's ileitis.     

Electron microscopic study of neuropeptide Y-containing nerve elements of the guinea pig small intestine

Neuropeptide Y-containing nerve cell bodies and processes were identified by electron microscopic immunocytochemistry in the guinea pig small intestine. Labeled nerve processes were numerous in the myenteric plexus. However, a few immunoreactive nerve fibers were found in all layers of the small intestine. Some of the immunoreactive nerve processes were found in close apposition to the epithelial cells of the crypts of Lieberkühn and to endothelial and smooth muscle cells. The neuropeptide Y-containing nerve cell bodies were preferentially located in the submucous ganglia. In the myenteric plexus many synaptic connections were observed between the neuropeptide Y-immunoreactive nerve fibers and unlabeled nerve cell bodies and other nerve fibers. These findings provide a morphologic basis for the possibility that neuropeptide Y may act as a transmitter and exert postsynaptic effects on intrinsic neurons, in addition to participating in the regulation of smooth muscle activity and epithelial cell functions.     

Abnormalities of nerve fibers in the circular muscle of patients with slow transit constipation

Abnormalities of the enteric nervous system are thought to explain the pathophysiology of motility disorders. Our aim was to determine if particular classes of enteric neurons are affected in slow transit constipation (STC). Specimens were taken from the terminal ileum and ascending, transverse and descending colon of patients undergoing subtotal colectomy for STC. Immunohistochemistry was performed using antisera to neuron-specific enolase, tachykinin, leu-enkephalin, choline acetyltransferase, vasoactive intestinal peptide, nitric oxide synthase, tyrosine hydroxylase and neuropeptide Y. The density of nerve fibres labelled with these antibodies in each layer was compared with age-matched controls. The density of nerve fibres with tachykinin and enkephalin immunoreactivity was reduced in the colonic circular muscle of the 15 patients with STC, whereas innervation of all other layers was normal. This reduction of tachykinin-immunoreactive nerve fibres also occurred in nine of the 12 specimens of terminal ileum examined. No difference was detected in the density or distribution of nerve fibres using the other antisera. Excitatory nerve fibres are present in the circular muscle in STC but they are deficient in tachykinins and enkephalin. Accepted: 14 January 1998     

Changes in adrenergic and peptidergic nerves in the submucous plexus of streptozocin-diabetic rat ileum.

The effect of streptozocin diabetes on the distribution of adrenergic and peptidergic nerves in the submucous plexus of rat ileum was investigated and compared with the changes in the myenteric plexus of the same region of ileum. There was an increase in the intensity of immunoreactivity in vasoactive intestinal polypeptide- and neuropeptide Y-like immunoreactive nerve fibers and neurons and a decrease in calcitonin gene-related peptide-like immunoreactivity but no change in substance P- and dopamine beta-hydroxylase-like immunoreactivity in the nerve fibers and neurons of the submucous plexus of both 8- and 16-wk streptozocin-diabetic rat ileum. However, in the myenteric plexus of the diabetic rat ileum, there was enlargement of varicosities and an increase followed by a slight decrease in the intensity of immunoreactivity of vasoactive intestinal polypeptide- and dopamine beta-hydroxylase-like immunoreactive nerve fibers and neurons, increased substance P-like immunoreactivity in diabetes at 16 wk, and an initial decrease (at 8 wk) followed by a recovery of calcitonin gene-related peptide-like immunoreactivity at 16 wk, but no change in neuropeptide Y-like immunoreactivity. The markedly different changes in peptidergic and adrenergic nerves between the two enteric plexuses show that diabetic neuropathy induced by streptozocin is not selective and involves factors other than neurotransmitter types.     

Oesophageal epithelial innervation in health and reflux oesophagitis

BACKGROUND: The response of the oesophagus to refluxed gastric contents is likely to depend on intact neural mechanisms in the oesophageal mucosa. The epithelial innervation has not been systematically evaluated in health or reflux disease. AIMS: To study oesophageal epithelial innervation in controls, and also inflamed and non-inflamed mucosa in patients with reflux oesophagitis and healed oesophagitis. PATIENTS: Ten controls, nine patients with reflux oesophagitis, and five patients with healed oesophagitis. METHODS: Oesophageal epithelial biopsy specimens were obtained at endoscopy. The distribution of the neuronal marker protein gene product 9.5 (PGP), and the neuropeptides calcitonin gene related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal peptide (VIP) were investigated by immunohistochemistry. Density of innervation was assessed by the proportion of papillae in each oesophageal epithelial biopsy specimen containing immunoreactive fibres (found in the subepithelium and epithelial papillae, but not penetrating the epithelium). RESULTS: The proportion of papillae positive for PGP immunoreactive nerve fibres was significantly increased in inflamed tissue when compared with controls, and non-inflamed and healed tissue. There was also a significant increase in VIP immunoreactive fibres within epithelial papillae. Other neuropeptides showed no proportional changes in inflammation. CONCLUSIONS: Epithelial biopsy specimens can be used to assess innervation in the oesophagus. The innervation of the oesophageal mucosa is not altered in non-inflamed tissue of patients with oesophagitis but alters in response to inflammation, where there is a selective increase (about three- to fourfold) in VIP containing nerves.     

Slow transit chronic constipation (Arbuthnot Lane's disease)

Seven patients (6 women, 1 man) with severe idiopathic chronic constipation, who underwent surgery with subtotal colectomy and ileorectal anastomosis, were investigated for the occurrence and density of nerve fibres, immunoreactive to different neuropeptides in the mucosa, submucosa, ganglia and smooth muscle in fresh specimens from the colon ascendens, the colon transversum and the colon descendens-sigmoideum. The following substances were studied: enkephalin, substance P, somatostatin, neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peptide, bombesin, motilin, tyrosine hydroxylase, dynorphin and galanin. Nerve fibres immunoreactive to CGRP occurred in large numbers in the myenteric ganglia of the patients with severe idiopathic chronic constipation, whereas in the myenteric ganglia of the control cases they only occurred in low numbers. In two patients there was no detectable motilin immunoreactivity and in one patient only sparse in the mucosa and the smooth muscle. The other neuropeptides investigated occurred in the density and distribution previously reported in the normal gut. With the present technique there were indications that patients with severe idiopathic chronic constipation have a significant difference in the occurrence of immunoreactive nerve fibres to CGRP and motilin compared to control patients.     

Beta cells are important for islet innervation: evidence from purified rat islet-cell grafts

Summary Pancreatic islets receive an extensive and complex innervation that includes sympathetic, nor-adrenergic nerve fibres also storing neuropeptide Y. Islets transplanted to the kidney capsule become progressively reinnervated, mainly by sympathetic fibres and to a lesser extent by parasympathetic and sensory fibres. The density of nerve fibres in the islet grafts is often higher than in the graft-bearing organ, suggesting that the grafted islets contain factors that promote ingrowth of nerve fibres. To find out if beta cells are of any importance for attracting nerve fibres, purified preparations of rat islet beta and non-beta cells were transplanted to the kidneys of nude mice. Some of the mice were rendered diabetic by alloxan injection before transplantation. Immunocytochemical analysis revealed that the beta-cell grafts became richly re-innervated by noradrenergic (tyrosine hydroxylase-containing) nerve fibres, also storing neuropeptide Y. Non-beta islet-cell grafts were virtually devoid of demonstrable nerve fibres. There was no discernible difference in the reinnervation pattern between diabetic and non-diabetic mice. The findings indicate that factors mediating islet neurotrophism are produced by the beta cellsAbbreviations NPY Neuropeptide Y - VIP vasoactive intestinal peptide - CGRP calcitonin gene-related peptide - SP substance P - PP pancreatic polypeptide - TH tyrosine hydroxylase     

Peptide-containing neurons in different regions of the submucous plexus of human sigmoid colon.

Specimens of the sigmoid colon were obtained from male and female patients (n = 11) with carcinoma of the colon or rectum and studied immunohistochemically for vasoactive intestinal polypeptide-, somatostatin-, substance P-, neuropeptide Y-, calcitonin gene-related peptide-, met- and leu-enkephalin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-containing nerves. In the subdivisions of the submucous plexus (namely, Schabadasch's, Meissner's, and the intermediate plexuses), substance P- and vasoactive intestinal polypeptide-immunoreactive nerve fibers were the most numerous, and equal densities of these nerves were found in all three layers. In contrast, few neuropeptide Y-, met-enkephalin-, leu-enkephalin-, calcitonin gene-related peptide-, somatostatin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-immunoreactive nerves were found in these regions. The nerve cell bodies of the submucous plexus contained vasoactive intestinal polypeptide, substance P, leu-enkephalin, somatostatin, and 5-hydroxytryptamine but not neuropeptide Y, met-enkephalin, calcitonin gene-related peptide, and dopamine beta-hydroxylase. Vasoactive intestinal polypeptide-containing nerve cell bodies were found in all three subdivisions. Substance P-, leu-enkephalin-, and somatostatin-immunoreactive nerve cell bodies were found in Schabadasch's plexus and the intermediate region of the submucous plexus, but they were absent from Meissner's plexus; 5-hydroxytryptamine-containing nerve cell bodies were only observed in Schabadasch's plexus. The possible function of the neuropeptide-, dopamine beta-hydroxylase-, and 5-hydroxytryptamine-containing neurons in the different layers of the submucous plexus is discussed.     

Primary oesophageal motility disorders: how primary are they?

The normal regulation of oesophageal peristalsis is complex. Nitric oxide-containing inhibitory neurons and cholinergic excitatory nerve fibres play the key roles. In the so-called primary oesophageal motility disorders, the coordination of oesophageal contractions and lower oesophageal sphincter function is disturbed (achalasia, diffuse oesophageal spasm), or the amplitudes of peristaltic contractions are abnormally high (nutcracker oesophagus). This article focuses on the pathophysiology of achalasia and nutcracker oesophagus. There is evidence that achalasia and nutcracker oesophagus should not be considered parts of one and the same range of diseases.     

Peptide-containing nerves in the rat femoral artery and vein. An immunocytochemical and vasomotor study

Peptide-containing nerves have been examined in the rat femoral artery and vein using immunocytochemical and vasomotor techniques. The general neuronal marker PGP 9.5 revealed a moderate supply of nerve fibres and fascicles forming a loose network in the adventitia and the adventitial-medial border of the artery and vein. The majority of the nerve fibres in both the artery and vein displayed immunoreactivity for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). The distribution pattern and number of these two types correlated well. The artery had a slightly richer PGP 9.5- immunoreactive nerve supply compared to the vein, but the nerve plexus in the vein displayed a more uniform arrangement. In contrast, relatively few nerve fibres displayed calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide immunoreactivity in either the artery or vein. The calcitonin gene-related peptide immunoreactive fibres had a similar distribution to that of the substance P containing fibres. Using a sensitive in vitro method the vasomotor responses to perivascular peptides were characterized. In the femoral artery NPY potentiated alpha 1-adrenoceptor mediated contractions, and had very little effect by itself. In contrast, 10(-7) M NPY contracted femoral veins by up to 68% relative to 60 mM potassium induced contraction, and there was no potentiation of alpha-adrenoceptor mediated contractions. Acetylcholine, peptide histidine isoleucine, vasoactive intestinal peptide, substance P and calcitonin gene-related peptide, all relaxed the contracted femoral artery and vein. Regarding the putative parasympathetic neurotransmitters, acetylcholine caused stronger relaxation of veins as compared to arteries whereas for vasoactive intestinal peptide and peptide histidine isoleucine the relaxations were stronger in the arterial preparation. These three agonists were more potent in the femoral vein. Substance P was more potent on the femoral vein, having the same maximum response in both preparations. On the other hand, the response induced by CGRP was some three times greater in the venous than in the arterial preparation. These data reveal that although there appear to be only minor differences in the peptidergic innervation of the rat femoral artery and vein pronounced differences occur in the peptide effector responses. The data support the concept that perivascular peptides play different roles in regulating various parts of the circulation.     

Achalasia like disorder of the oesophagus in von Recklinghausen's neurofibromatosis.

The association of achalasia like disorder of the oesophagus with von Recklinghausen's neurofibromatosis to our knowledge not previously reported is described in a 56 year old man who also had bladder dysfunction. At necropsy the oesophageal myenteric plexus showed ganglion cell depletion with nerve fibre hyperplasia probably the result of Schwann cell hyperplasia. We suggest that the disturbances of oesophageal and bladder function were a consequence of involvement of the autonomic nervous system by neurofibromatosis.     

Nitric oxide synthase in neurons of the human gall-bladder and its colocalization with neuropeptides

The distributions of nerve cells and fibres that are immunoreactive for nitric oxide synthase (NOS) have been investigated in the human gall-bladder. In addition, the colocalization of NOS immunoreactivity (IR) with neuropeptide Y (NPY), pituitary adenylyl cyclase activating peptide (PACAP), somatostatin (SOM), substance P (SP), tyrosine hydroxylase (TH) and vasoactive intestinal peptide (VIP)-IR was determined. Nitric oxide synthase-IR nerve cell bodies comprised 13 and 30% of nerve cells in ganglia of the fibromuscular and subepithelial layers, respectively. To determine these percentages, neuron-specific enolase-IR was used as a marker for all nerve cells. Although SOM- and VIP-IR nerve cell bodies were found in both ganglia, they rarely contained NOS-IR. In the fibromuscular layer, NOS-IR nerve fibres were abundant and most PACAP-, SOM- and VIP-IR fibres and many NPY-IR fibres were also NOS positive. No colocalization was observed between NOS- and SP- or TH-IR. In the mucosal layer, moderate numbers of NOS-IR fibres were found and the degree of colocalization of NOS-IR with each of NPY-, PACAP-, SOM-, SP- and VIP-IR were as follows: PACAP and NPY > VIP > SOM and SP. Nitric oxide synthase and TH were not colocalized in mucosal fibres. These results suggest that nerve fibres in the fibromuscular layer in the human gall-bladder with the chemical coding NOS/NPY/PACAP/SOM/VIP are axons of inhibitory motor neurons. Nitric oxide synthase-IR fibres in the mucosal layer that contained NPY, PACAP, SOM, SP and VIP with various degrees of colocalization probably contribute to the control of epithelial secretion or absorption.     

Origins of peptide and norepinephrine nerves in the mucosa of the guinea pig small intestine

Norepinephrine, acetylcholine, and certain peptides are contained in mucosal nerves and have potent effects on transepithelial water and electrolyte fluxes. It is difficult to ascribe roles for these nerves as their sources are unknown. The present studies were undertaken to determine the origins of nerve fibers that are found in the mucosa of the guinea pig small intestine and which contain one of the following substances: vasoactive intestinal peptide, substance P, somatostatin, neuropeptide Y, cholecystokinin, or norepinephrine. Nerve fiber origins were ascertained by making lesions to sever pathways through which the nerves could reach the mucosa. The lesioning operations were homotopic autotransplants of short (2 cm) segments of intestine; myectomies, in which a 5-10-mm length of intestine was stripped of longitudinal muscle and myenteric plexus; and extrinsic denervation, in which nerves reaching the intestine through the mesentery were severed. The results of these studies, considered along with previously published work, led to the upcoming conclusions. Nerve fibers in the mucosa showing immunoreactivity for vasoactive intestinal peptide, somatostatin, cholecystokinin, and neuropeptide Y arise from cell bodies in the overlying submucous plexus. Substance P fibers arise in part from the overlying submucous plexus and in part from the overlying myenteric plexus. Mucosal norepinephrine fibers arise from extrinsic sympathetic ganglia. Enkephalin, gastrin-releasing peptide, and 5-hydroxytryptamine, which are in some enteric nerves, are not found in submucous nerve cells and few, if any, fibers containing these substances supply the mucosa. Thus, the mucosa receives a dense nerve supply, much of which arises locally from submucous ganglia.     

Vasoactive intestinal peptide immunoreactive nerve fibres are deficient in intestinal and nasal mucosa affected by cystic fibrosis

Cystic fibrosis (CF) is the most common lethal or debilitating inherited disease amongst Caucasians, with estimates of its frequency of occurrence in this population ranging from 1: 2000 to 1: 15 000 live births. It is characterized by disorders of exocrine secretions, primarily of the skin, respiratory tract and digestive system. The secretory processes of these tissues are influenced by autonomic nerve fibres, many of which contain regulatory peptides. The innervation of the intestinal and respiratory mucosa of CF patients has been investigated in order to determine if there is any derangement of the peptide-containing nerve fibres that supply these tissues. The present work demonstrates that, in CF, there is a deficiency of vasoactive intestinal peptide immunoreactivity (VIP-IR) in nerve fibres in the nasal and intestinal mucosa. There is not a generalized loss of fibres that are immunoreactive for this peptide, however, since VIP-IR fibres innervating the intestinal muscle are largely unaffected. Moreover, other types of nerve fibres innervating the nasal mucosa and the mucosa of the intestinal villi appear to be unaffected in CF patients. Physiological evidence indicates that vasoactive intestinal peptide is contained in secretomotor neurons and is a powerful stimulant of secretion; loss of function restricted to these neurons is consistent with the clinical manifestations of CF.     

Migration of the myoelectric complex after interruption of the myenteric plexus: intestinal transection and regeneration of enteric nerves in the guinea pig

The effects of surgical interruption of the myenteric plexus (myectomy), extrinsic denervation of a length of small intestine, or transection and reanastomosis of the intestinal wall on migration of phase III of the migrating myoelectric complex was studied in guinea pigs. In addition, the recovery of phase III migration and the regrowth of intestinal nerves and muscle across the reanastomosis was studied at various times up to 60 days after surgery. At 6-9 days after surgery, phase III did not migrate past the myectomy during 50%-60% of recorded migrating myoelectric complexes and transection and reanastomosis of the intestinal wall blocked aboral progression of phase III in 90% of cases. Extrinsic denervation did not alter phase III migration through the denervated segment. Phase III migration past the reanastomosis recovered with time after surgery; 80% recovery occurred by 60 days after surgery. Immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin were used as markers for intestinal nerves that were cut by transaction. Immunoreactivities for vasoactive intestinal peptide and gastrin-releasing peptide are contained in myenteric neurons that project in an oral to anal direction to other myenteric ganglia and to the circular muscle. Immunoreactivity for somatostatin is contained in nerve fibers projecting aborally to other myenteric ganglia. At 7-15 days after surgery, there were accumulations of immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin in nerve fibers on the oral side of the reanastomosis, but nerve fibers containing these peptides were not observed in myenteric ganglia or circular muscle close to the anal edge. At 23-28 days, immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin nerve fibers were traced across the reanastomosis and nerve terminals were detected in ganglia and muscle close to the lesion on the anal side. Nerve fibers traversed the lesion in all cases at 57-60 days and vasoactive intestinal peptide-, gastrin-releasing peptide-, and somatostatin-immunoreactive nerve terminals were detected in the first two to three rows of myenteric ganglia on the anal side. Regrowth of intestinal muscle followed a similar time-course to that observed for nerves. These data suggest that interruption of the myenteric plexus alone does not completely block phase III migration. In addition, recovery of phase III migration past a reanastomosis is associated with a restoration of both nervous and mechanical connections.     

Distribution and origin of the peripheral innervation of rat cervical esophagus

Several neurotransmitters, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), galanin, enkephalin, calcitonin-gene related peptide (GGRP), substance P, as well as nitric oxide synthase (NOS), and the noradrenergic marker tyrosine-hydroxylase (TH) were localized by immunocytochemistry in the cervical esophagus of rat. Nerve fibers containing the neuropeptides, NOS, and TH were distributed in the myenteric plexus, around muscle bundles and small blood vessels. Injection of the retrograde tracer True Blue (TB) into the cervical esophagus resulted in the appearance of labeled nerve cell bodies in the superior cervical, the stellate, the nodose, the sphenopalatine, the dorsal root ganglia at levels C₂–C₇, and in local ganglia close to the thyroid. Most of the TB-labeled nerve cell bodies in the superior cervical ganglia contained NPY. In the stellate ganglion, a few labeled nerve cell bodies contained VIP whereas an additional few cell bodies stored NPY. In local ganglia, the majority of labeled cell bodies contained VIP. In the nodose ganglion and cervical dorsal root ganglia, the majority of the labeled nerve cell bodies stored CGRP. The results indicate that the cervical esophagus has a dense innervation with multiple neurotransmitters emanating from several ganglia. As judged by the pattern of nerve fiber distribution, they may regulate esophageal peristalsis and blood flow, some of them possibly in a cooperative manner.     

Vasoactive-intestinal-peptide- and substance-P-immunoreactive nerve fibres in the myenteric plexus of mouse colon during the chronic phase of Trypanosoma cruzi infection.

The distribution of a tachykinin (substance P) and vasoactive intestinal peptide (VIP) and the number and morphology of the large granular vesicles (LGV) in the myenteric plexus of the colons of mice were investigated. Six of the 12 young, male, Swiss mice studied had been inoculated with the Y strain of Trypanosoma cruzi 2 months previously whereas the others were uninfected controls. Substance P (SP) and VIP were localized by light microscopy, using an immunohistochemical method, and LGV were counted in sections studied by electron microscopy. There were far fewer LGV and less intensely staining varicose VIP- and SP-positive nerve fibres in the infected mice than in the controls. Denervation of the myenteric plexus may decrease the content of tachykinins (TK) and VIP in animals infected with T. cruzi. Such reduction in TK and VIP activity could be related to the disturbances in intestinal motility observed in the chronic phase of Chagas disease.