Coeliac-superior Mesenteric Ganglion Research Articles

Vagal and splanchnic sensory pathways mediate inhibition of gastric motility induced by duodenal distension.

Afferent pathways mediating gastric corpus relaxation after duodenal distension were studied in urethan-anesthetized rats in which the sensory neurotoxin capsaicin (1%) or its vehicle was applied directly to the cervical vagus nerve trunks or the celiac-superior mesenteric ganglia 10-20 days before experiments. Distension (0.05-0.5 ml) of a closed loop of proximal duodenum decreased gastric intraluminal pressure. Perineural capsaicin treatment to the vagus nerves decreased by 73 and 80% the response to low volumes of distension (0.05 and 0.1 ml). Perineural capsaicin treatment of the celiac-superior mesenteric ganglia significantly attenuated by 46-88% the response to all volumes of distension. Bilateral cervical vagotomy or ganglionectomy reduced the response to all volumes of duodenal distension and, in combination, abolished the response. It is concluded that the decrease in gastric corpus motility after duodenal distension is dependent on the extrinsic innervation to the upper gastrointestinal tract and is mediated by both vagal and spinal capsaicin-sensitive afferents. Capsaicin-sensitive vagal afferents mediate responses to low volumes of distension that may be physiological. Capsaicin-sensitive spinal afferents mediate the gastric response to higher volumes of distension and may be involved in mediating visceral and somatic responses to pathophysiological intestinal obstruction.

Gastric mucosal hyperemia due to acid backdiffusion depends on splanchnic nerve activity.

Acid backdiffusion through a disrupted gastric mucosal barrier leads to an increase in gastric mucosal blood flow (MBF). This response involves afferent neurons that pass through the celiac ganglion. The present study examined the neural pathways that underlie the rise in MBF caused by gastric perfusion with 15% ethanol in 0.15 N HCl. MBF was measured by the hydrogen gas clearance technique in urethan-anesthetized rats. Mucosal hyperemia due to acid backdiffusion was not changed by acute bilateral subdiaphragmatic vagotomy but was blocked by acute removal of the celiac-superior mesenteric ganglion complex or acute bilateral transection of the greater splanchnic nerves. Hexamethonium (85 mumol/kg iv) also attenuated the rise in MBF due to acid backdiffusion, whereas guanethidine (0.225 mmol/kg sc) had no effect. None of the procedures and drug treatments altered basal MBF to a significant extent. Transection of the splanchnic nerves, hexamethonium, and guanethidine lowered mean arterial blood pressure, but hypotension as such did not significantly influence the hyperemic response under study. Taken together, the previous and present data indicate that the rise in MBF caused by acid backdiffusion depends on the integrity of afferent and efferent neural pathways that run in the splanchnic nerves and through the celiac ganglion. The efferent pathway involves ganglionic transmission through nicotinic acetylcholine receptors but is independent of noradrenergic neurons.

Differential effect of streptozotocin-induced diabetes on the innervation of the ileum and distal colon

The effect of short-term and long-term streptozotocin-induced diabetes on the pattern of distribution and tissue content of adrenergic and peptidergic nerves in ileum and distal (descending) colon of the rat was examined using immunohistochemical, biochemical, and immunochemical techniques. The effect of short-term streptozotocin-induced diabetes on the level of noradrenaline compared with weightrestricted (starved) and untreated controls in the celiac (celiac-superior mesenteric ganglia complex) and inferior mesenteric ganglia, which supply the two regions of the intestine, was also compared. The pattern of change in the distribution of dopamne-β-hydroxylase-, substance P-, calcitonin gene-related peptide-, and vasoactive intestinal polypeptide-like immunoreactive nerve fibres that was observed in the ileum from diabetic rats was not evident in the myenteric plexus of distal colon. In contrast to the ileum, there was no evidence of degenerative change in any of the nerve types investigated in the myenteric plexus of the distal colon. The level of vasoactive intestinal polypeptide in the diabetic rat ileum was significantly increased, whereas the level of noradrenaline was reduced; no such changes were observed in the distal colon. The tissue content of noradrenaline in the celiac ganglion, which projects to the ileum, was increased at 8-week diabetes compared with both weight-restricted and untreated controls, whereas the diabetic state had no effect on the levels of noradrenaline of the inferior mesenteric ganglion, which projects to the distal colon. It is concluded that there is a differential effect of streptozotocin-diabetes on different regions of the rat intestine. The adrenergic and peptidergic innervation of the distal colon were changed little compared with ileum. This may be explainable in terms of the different functional roles of these two regions of the intestine and/or by the difference in origin of the sympathetic nerves supplying the two regions of the intestine.

The target specificity of the extrinsic innervation of the rat small intestine

The target specificity of the extrinsic innervation of the rat small intestine was examined by simultaneously injecting the proximal and distal small intestine with either wheat germ agglutinin-horseradish peroxidase (HRP) or fast blue. The number of single- and double-labeled cells in the nodose, dorsal root and coeliac-superior mesenteric ganglia and the dorsal motor nucleus of the vagus were counted and expressed as percentages of total labeled cells. Cells containing both HRP and Fast blue projected to both regions of the intestine. We found that the nodose and mesenteric ganglia contained significantly fewer double-labeled neurons (approximately 3 and 9% respectively) than the dorsal motor nucleus (19%) or dorsal root ganglion (20%). Presumably, a large number of double-labeled afferent or efferent neurons would limit the ability of a given component of the extrinsic innervation to control the activity of restricted regions of the small intestine (but might be important in overall regulation of intestinal function). In a separate series of experiments we examined the topography of neurons in the dorsal motor nucleus of the vagus labeled with HRP injection into either the proximal or distal small intestine. Both of these injections labeled neurons in the entire rostro-caudal extent of the nucleus, though approximately 75% of the cells were located between 720 microns caudal and 720 microns rostral to the obex. Cells in the rostral regions were found primarily in the lateral pole of the nucleus, whereas caudal regions contained labeled cells in both the medial and lateral poles.

After-depolarization of sympathetic neurons in rat coeliac-superior mesenteric ganglia and its modulation by tachykinins

After-depolarization of sympathetic neurons in rat coeliac-superior mesenteric ganglia and its modulation by tachykinins

Immunohistochemical localization of 5-hydroxytryptamine, histamine and histidine decarboxylase in the rat major pelvic and coeliac-superior mesenteric ganglion

The localization of 5-hydroxytryptamine (5-HT), histamine and histidine decarboxylase (HDC), the enzyme synthesizing histamine, was studied in the rat major pelvic and coeliac-superior mesenteric ganglia by an indirect immunofluorescence technique. Small cells (10–20 μm in diameter) exhibiting 5-HT, histamine or HDC immunoreactivities were observed in clusters or occurred as solitary cells in both ganglia. In the major pelvic ganglia, solitary histamine-immunoreactive principal neurons were also observed. Colocalization studies indicated that all 5-HT-, histamine- and HDC-immunoreactive small cells in these ganglia were labelled with tyrosine hydroxylase (TH), suggesting that they are small intensely fluorescent (SIF) cells. In the coeliac-superior mesenteric ganglia, all TH-immunoreactive SIF cells were also intensely immunoreactive for 5-HT and HDC. In the major pelvic ganglia, all TH-immunoreactive SIF cells contained 5-HT immunoreactivity, and the majority of them were also intensely immunoreactive for HDC. In both ganglia, however, only a subpopulation of TH-immunoreactive SIF cells displayed histamine immunoreactivity. The results indicate that in the rat major pelvic and coeliac-superior mesenteric ganglia, a population of catecholamine-containing SIF cells contain 5-HT and histamine suggesting a diverse role SIF cells may have in so far as modulation of ganglion transmission is concerned.

Development of a quantitative histochemical method for determination of succinate dehydrogenase activity in autonomic neurons and its application to the study of aging in the autonomic nervous system.

An accurately validated method was developed for quantitative determination of succinate dehydrogenase (EC 1.3.99.1; SDH) activity in individual sympathetic neuron perikarya by microdensitometric measurement of an SDH-nitroblue tetrazolium-derived formazan final reaction product. Optimal incubation medium and reaction conditions were determined for measurement of reaction product in cryostat sections of rat superior cervical and celiac-superior mesenteric ganglia. The Beer-Lambert laws were verified for the ganglion tissue, and microdensitometric measurements (expressed as mean cell density readings; MCDR/min-1), characteristic of the Michaelis-Menten equation, enabled the results to be used for enzyme kinetic determinations of SDH activity. Km and Vmax values were obtained following Hans linear transformation of the readings. Between the ages of 6-24 months no significant variations in Km values were recorded, indicating an unchanged structure for SDH (overall mean Km = 0.083 +/- 0.055 mM). However, in both ganglia there were significant decreases (ranging from 43-54%) in Vmax values for SDH at 24 months. The overall mean Vmax value at 6 months was 4.01 +/- 0.61 (MCDR) and at 24 months was 2.07 +/- 0.76 (MCDR). This suggests that an overall decrease in metabolic activity takes place with age in sympathetic neurons of the rat superior cervical and celiac-superior mesenteric ganglia.

An ultrastructural study of dynorphin-immunoreactive nerve fibers and terminals in the celiac-superior mesenteric ganglion of the guinea pig

Dynorphin-immunoreactive nerve fibers and terminals were identified in the celiac-superior mesenteric ganglion of the guinea pig at the ultrastructural level with the peroxidase-antiperoxidase technique. The immunostained material was localized in the large dense core vesicles of the terminals but was also present diffusely in the axoplasm. The terminals formed numerous axodendritic and a few axosomatic contacts, interpreted as synapses, with the principal ganglion cells. These findings suggest that dynorphin plays a role as a neurotransmitter or neuromodulator in the ganglion and, taken together with earlier findings, indicate an involvement of dynorphin neurons in the intestino-intestinal inhibitory reflex.

Morphometric studies on the microvasculature of pre- and paravertebral sympathetic ganglia in the adult and aged rat by light and electron microscopy.

Morphometric measurements have been made by light and electron microscopy on sections of perfused sympathetic ganglia from rats of 6-24 months of age with special reference to the microvascular bed. Capillaries, postcapillary venules and small venules comprised the majority of the vessels studied but small arterioles were, in addition, included in the light microscopical part of the study. Light microscopical measurements using image analysis showed that there was a decrease in the density of the microvascular bed (number of vascular profiles/area) and in the total vascular luminal area with age in both ganglia. The ratio of neurons to microvessels remained constant in the superior cervical ganglion (SCG) but decreased with age in the coeliac-superior mesenteric ganglion (CSMG). However, the distribution of microvessels in relation to individual neurons remained unchanged throughout life in both ganglia. Ultrastructural studies revealed fenestrations in 12% of SCG microvessel profiles and in 38% of CSMG microvessels at 6 months, but the percentage of fenestrated profiles in the CSMG had declined by 24 months. There were no significant differences in the number of fenestrations per fenestrated profile. The basal lamina surrounding the microvessels increased significantly (almost doubling) in thickness with age. The range and distribution of microvessel wall thicknesses, expressed as harmonic mean wall thickness, were comparable in both ganglia at both ages and increased linearly according to the amount of pericyte covering present. No consistently significant relationships could be discerned between the microvessel wall thickness and luminal diameter or between the wall thickness and the area available to a given volume of blood for exchange of metabolites (luminal perimeter/luminal area). We conclude that the ganglionic capillary bed is similar in both ganglia and, in old age, accommodates structural changes that occur in the ganglion by maintaining its structure and relationship to individual neurons.

L-glutamate decarboxylase immunoreactivity in developing sympathetic tissues of the rat

An indirect immunofluorescence method was used to study the appearance and distribution of l-glutamate decarboxylase (GAD), the enzyme synthesizing γ-aminobutyric acid, in developing rat retroperitoneal sympathetic tissues. GAD immunoreactivity was analyzed in correlation with immunoreactivity to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), in the main retroperitoneal paraganglion, adrenal medullae and abdominal sympathetic ganglia. In different abdominal sympathetic tissues TH-immunoreactive cells first appeared on embryonic days 12.5–14.5, while GAD immunoreactivity was first observed in all these tissues in 14.5-day-old embryos (E 14.5). This suggests that the first expression of GAD is not coupled to the onset of catecholamine synthesis. In developing chain ganglia, GAD immunoreactivity was localized prenatally only in cell clusters with bright TH immunoreactivity, suggesting that GAD is expressed only in the cell lineage leading to ganglionic small intensely fluorescent (SIF) cells. The coeliac-superior mesenteric ganglion complex developed from the preaortic sympathetic tissue, starting from E 16.5 embryos, when the cranial, moderately TH-immunoreactive cells of this tissue were seen to form compact cell islets around the branches of the abdominal aorta. The caudal, intensely TH-immunoreactive cells of preaortic sympathetic tissue were seen to form the main retroperitoneal paraganglion from day E 15.5. During the prenatal period GAD immunoreactivity in preaortic sympathetic tissue was present caudally only in these paraganglionic cells and cranially in some brightly TH-immunoreactive cells, representing SIF and/or paraganglionic cells. In the adrenal medulla, only some of the TH-immunoreactive cells showed GAD immunoreactivity during early developmental stages. The moderately TH-immunoreactive, noradrenaline-synthesizing, cell clusters were seen for the first time in E 16.5 embryos, and they exhibited no GAD immunoreactivity. Thereafter, GAD was expressed only in the intensely TH-immunoreactive, adrenaline-synthesizing, cell clusters. The results of this study indicate that in the developing rat sympathetic tissues GAD is present only in the cell lineages which differentiate into SIF cells of abdominal sympathetic ganglia, preaortic paraganglionic cells and adrenaline cells of the adrenal medulla.

Distribution of peptidergic terminals of enteric origin in the rat celiac ganglion

We examined the distribution of enterofugal nerve terminals of bombesin-, cholecystokinin- and vasoactive intestinal polypeptide-like immunoreactivity in the rat celiac-superior mesenteric ganglion complex. The majority of these nerve terminals were concentrated in the mesenteric side of the ganglion. The present findings suggest that some functional specialization occurs in the celiac ganglion of the rat.

Tachykinins produce fast and slow depolarizations in sympathetic neurons of rat coeliac-superior mesenteric ganglia

The actions of mammalian tachykinins on neurons of rat coeliac-superior mesenteric ganglia (C-SMG) were examined using intracellular recording in isolated preparations. Application of substance P, neurokinin A and neurokinin B produced fast and slow depolarizations in the ganglion cells. The two responses were clearly distinguishable in their electrophysiological characteristics. The results suggest that different receptor mechanisms are involved in fast and slow depolarizing actions of tachykinins in rat C-SMG cells.

Measurements of the DNA amount in mono- and binucleate cells in the celiac superior mesenteric ganglion of the guinea pig.

The relative proportion, ultrastructure and DNA-content of the binucleate cells in the celiac superior mesenteric ganglion of the guinea pig was studied using light and electron microscopy as well as computerized image analysis of Feulgen stained cells. The number of mono - versus binucleate cells was found to vary with stage of development with about 40% of the cells being binucleate in adult animals and 50% in late prenatal stage. No difference in ultrastructure was observed between the nuclei of the two cell types. The binucleate cells contain twice the amount of DNA found in the mononucleate cells.

An electron microscopic study on VIP-, BOM- and CCK-like immunoreactive terminals in the celiac-superior mesenteric ganglion complex of the guinea pig

The distribution and fine structure were studied of the following 3 peptide-containing fibers of enteric origin, vasoactive intestinal polypeptide (VIP), bombesin (BOM) and cholecystokinin (CCK)-like immunoreactive peptide in the celiac-superior mesenteric ganglion complex (CMG) of the guinea pig. These peptides, especially VIP, were distributed more densely on the mesenteric side than on the celiac side of the CMG, and their distribution shared a similar mosaic pattern. Immunoelectron microscopic analysis revealed that the fibers formed synaptic contacts with the proximal dendrites of the principal ganglion cells, however, the profiles of these synaptic junctions differed between fibers. Those containing VIP or CCK formed symmetrical synapses, while those containing BOM formed assymetrical ones. This suggests that there are some functional differences between these enterofugal fibers in the CMG.

Simultaneous immunohistochemical demonstration of intra-axonally transported markers and neuropeptides in the peripheral nervous system of the guinea pig

Projections and peptide neurotransmitter/neuromodulator content of autonomic and visceral afferent neurons of the guinea pig were studied after application of the subunit B of cholera toxin (CTB) with or without horseradish peroxidase (HRP) as retrograde and anterograde tracers and subsequent immunohistochemical processing for double staining using antibodies raised to CTB, HRP and various neuropeptides. The results demonstrate that substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing dorsal root ganglion cells project to the pylorus as well as to the celiac superior mesenteric and stellate ganglia as demonstrated with both retrograde and anterograde transport methodology. Binding studies revealed that a small number of the CTB-binding dorsal root ganglion cells contains immunoreactivity to SP and CGRP. The majority of the CTB-binding cells is SP- and CGRP-negative and terminate in the deeper parts of the dorsal horn. After injection of CTB conjugated to HRP (B-HRP) into the nodose ganglion, both motor and sensory elements were labeled in the medulla oblongata. Some of the CTB labeled vagal sensory nerve fibers in the nucleus tractus solitarii (NTS) were also found to contain immunoreactivity to SP or CGRP. The tracer was also transported through the peripheral branch of the nodose ganglion cells and labeled terminals in the esophagus.

Localization of bombesin-, neuropeptide Y-, enkephalin-and tyrosine hydroxylase-like immunoreactivities in rat coeliac-superior mesenteric ganglion

The localization of bombesin- (BOMB) and enkephalin- (ENK) immunoreactive (IR) nerves was studied in rat coeliac-superior mesenteric ganglion complex in relation to neuropeptide Y (NPY)- and tyrosine hydroxylase (TH)-immunoreactive neurons with an immunofluorescence double-staining method. Very dense networks of BOMB-IR nerve terminals surrounded the majority of the principal ganglion cells, whether or not they were TH-IR. BOMB-IR nerves were specifically related to the non-NPY-IR neurons. Moderately dense networks of ENK-IR fibers were unevenly distributed among the ganglion cells. Majority of these neurons exhibited TH-IR and some of them also contained NPY-IR. In sections double stained with antibodies to ENK and BOMB some nerve fibers contained both peptides. The findings suggest that BOMB-IR nerves, which have been previously demonstrated to originate from gut, control the function of non-NPY-IR ganglion cells. ENK-IR nerves apparently control the adrenergic neurons which project to gut and also some NPY-IR vasomotoric neurons. The finding that ENK- and BOMB-IR coexist in some nerves suggests that some ENK-IR nerves may originate from gut, although the major part probably represents preganglionic fibers originating from spinal cord.

Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa

Ablation of capsaicin-sensitive afferent neurons enhances experimentally induced ulceration in the rat gastric mucosa, which suggests that these neurons are involved in gastric mucosal protection. To provide direct evidence for such a function it was investigated whether stimulation of afferent nerve endings by the intragastric administration of capsaicin could counteract the ulcerogenic effect of 25% ethanol. Capsaicin (3.2–640μM), administered together with ethanol, inhibited the development of haemorrhagic lesions in a concentration-dependent fashion but did not alter the ethanol-induced fall in the gastric potential difference. This suggests that capsaicin does not prevent ethanol from damaging gastric epithelial cells but can counteract the vascular lesions caused by ethanol. The anti-lesion effect of intragastric capsaicin was absent in adult rats which had been treated with a high dose of systemic capsaicin as neonates in order to achieve a permanent degeneration of unmyelinated afferent neurons. It would appear, therefore, that intragastric capsaicin reduces lesion formation by an action on afferent neurons. The protective effect of intragastric capsaicin was not altered following acute subdiaphragmatic vagotomy, acute removal of the coeliac-superior mesenteric ganglion complex, acute bilateral ligation of the adrenal glands, or pretreatment of the rats with atropine or guanethidine. These findings indicate that stimulation of afferent neurons by intragastric capsaicin affords protection of the rat gastric mucosa against ethanol-induced damage. As the autonomic nervous system is not involved gastroprotection appears to represent a local effector function of sensory nerve endings in the stomach.

Sympathetic and afferent neurons projecting in the splenic nerve of the cat

Afferent and sympathetic postganglionic nerve cell bodies projecting in the splenic nerve of the cat have been labeled retrogradely with horseradish peroxidase (HRP) in order to study numbers and locations of these neurons. Labeled somata were found bilaterally in dorsal root and sympathetic paravertebral ganglia T3-L2 with a maximum in T10-T13 and in the coeliac superior mesenteric ganglion complex. About 13,200 neurons project into the splenic nerve of the cat, 12,550 being postganglionic and 650 afferent. About 98% of the postganglionic neurons were located in prevertebral and 2% in paravertebral sympathetic ganglia. About 73% of the afferent and 66% of the postganglionic paravertebral neurons were located on the left side. The density of the splenic innervation is about 3-4 times higher than that of the kidneys when normalized to the weight of both organs. It is discussed whether the afferent and sympathetic innervation of the spleen is not only involved in cardiovascular functions but also in regulation of the immune response of this organ.

Distribution and origin of peptide-containing nerve fibers in the celiac superior mesenteric ganglion of the guinea-pig

The origin of the peptidergic nerve fibers and terminals in the celiac superior mesenteric ganglion of the guinea-pig was studied. The distribution of immunoreactivity to enkephalin, substance P, calcitonin gene-related peptide, cholecystokinin, vasoactive intestinal polypeptide/peptide histidine isoleucine, bombesin and dynorphin was analysed in intact animals and in animals subjected to various denervation and ligation procedures. The present results show that each of the connected nerve trunks carries peptidergic pathways and contributes to the peptidergic networks in the celiac superior mesenteric ganglion. Thus, the thoracic splanchnic nerves contain enkephalin-, substance P- and calcitonin gene-related peptide-immunoreactivity of which substance P and calcitonin gene-related peptide coexist in the same nerve fibers. In addition, cholecystokinin-, vasoactive intestinal polypeptide/peptide histidine isoleucine- and dynorphin-immunoreactivity is present in some fibers. All of these immunoreactivities are present in sensory neurons except enkephalin which probably originates in the spinal cord. The mesenteric nerves carry enkephalin-, calcitonin gene-related peptide-, cholecystokinin-, vasoactive intestinal polypeptide/peptide histidine isoleucine-, bombesin- and dynorphin-immunoreactive fibers from the intestine and are the main source for cholecystokinin, vasoactive intestinal polypeptide/peptide histidine isoleucine, bombesin and dynorphin fibers. Double-staining experiments indicate that many of these peptides are synthesized in the same enteric neurons. Also the intermesenteric nerve contains peptide-immunoreactive fibers to the celiac superior mesenteric ganglion from different sources, probably including the distal colon as well as dorsal root ganglia and spinal cord at lower thoracic and lumbar levels. The results are discussed in relation to earlier morphological and physiological studies supporting the view of a role of the celiac superior mesenteric ganglion in local reflex mechanisms involved in regulation of gastrointestinal functions.

Cholecystokinin inhibits gastric motility and emptying via a capsaicin-sensitive vagal pathway in rats

The pathway by which cholecystokinin octapeptide (CCK-8) inhibits motility of the proximal stomach and the role of this pathway in the CCK-induced delay in gastric emptying of a liquid meal has been studied in rats by selective destruction of vagal afferent C-fibers using bilateral perineural application of the sensory neurotoxin, capsaicin, 3 or 4 days prior to the experiment. The capsaicin treatment significantly attenuated the decrease in intragastric pressure in urethan-anesthetized rats in response to CCK-8 (0.1-100 pmol iv) compared with vehicle-treated controls. Removal of the celiac-superior mesenteric ganglion completely abolished the inhibitory action of CCK-8 on gastric motility in these rats. In contrast, only celiac ganglionectomy in combination with vagotomy abolished the CCK-8 effect in vehicle-treated controls. Intravenous injection of CCK-8 (300 pmol) 5 min before intragastric administration of a methylcellulose solution decreased gastric emptying by 55% in conscious control or vehicle-treated rats. Perivagal capsaicin treatment abolished the delay in gastric emptying induced by CCK-8. In addition, capsaicin treatment alone significantly increased gastric emptying. These results demonstrate that CCK-8 decreases gastric motility in the gastric corpus and delays gastric emptying by a capsaicin-sensitive vagal afferent pathway. These same afferent fibers may also play a physiological role in the gastric emptying of liquids.