The locations of cell bodies of sympathetic neurons projecting to the stomach, the duodenum, the ileum, the colon, the spleen and the pancreas have been studied using retrograde tracing. Projections arose from both pre- and paravertebral ganglia. In the rat, the prevertebral ganglia are the paired coeliac ganglia lying caudo-lateral to the root of the coeliac artery, paired splanchnic ganglia in the abdominal segments of the greater splanchnic nerves, unpaired superior mesenteric and inter-renal ganglia and the inferior mesenteric ganglia. The projections from the prevertebral sympathetic ganglia to the different parts of the gut were organised somatotopically. The most rostral ganglia (splanchnic, coeliac, and superior mesenteric ganglia) contained neurons innervating all regions of the gastrointestinal tract, the pancreas and the spleen. The inter-renal and inferior mesenteric ganglia, located more caudally, contained neurons innervating the distal part of the gut (distal ileum and colon). The innervation of the spleen and the pancreas came from the closest ganglia (sympathetic chains, splanchnic and coeliac ganglia). This organotopic organisation was not found in the sympathetic chain ganglia; the innervation of all organs came predominantly from the lower part of the thoracic chains. A large proportion of the retrogradely labelled nerve cells in the splanchnic ganglia received nitric oxide synthase immunoreactive innervation probably from the spinal cord. In the other prevertebral ganglia, most of the neurons received nitric oxide synthase immunoreactive innervation and/or bombesin immunoreactive innervation. This leads to the conclusion that, in these ganglia, many neurons receive projections from the gastrointestinal tract in addition to the spinal cord.

Previous studies have identified Dogiel type II neurons with cell bodies in the myenteric plexus of guinea-pig ileum to be intrinsic primary afferent neurons. These neurons also have distinctive electrophysiological characteristics (they are AH neurons) and 82-84% are immunoreactive for calbindin. They are the only calbindin-immunoreactive neurons in the plexus. Neurons with analogous shape and electrophysiology are found in submucosal ganglia, but, with antibodies used in previous studies, they lack calbindin immunoreactivity. An antiserum that is more effective in revealing calbindin in the guinea-pig enteric nervous system has been reported recently. In the present work, we found that this antiserum reveals the same population that was previously identified in myenteric ganglia, and does not reveal any further population of myenteric nerve cells. In submucosal ganglia, 9-10% of nerve cells were calbindin immunoreactive with this antiserum. The submucosal neurons with calbindin immunoreactivity were also immunoreactive for choline acetyltransferase, but not for neuropeptide Y (NPY) or vasoactive intestinal peptide (VIP). Small calbindin-immunoreactive neurons (average profile 130 microm2) were calretinin immunoreactive, whereas the large calbindin-immunoreactive neurons (average profile 330 microm2) had tachykinin (substance P) immunoreactivity. Calbindin immunoreactivity was seen in about 50% of the calretinin neurons and 40% of the tachykinin-immunoreactive submucosal neurons. It is concluded that, in the guinea-pig ileum, only one class of myenteric neuron, the AH/Dogiel type II neuron, is calbindin immunoreactive, but, in the submucosal ganglia, calbindin immunoreactivity occurs in cholinergic, calretinin-immunoreactive, secretomotor/vasodilator neurons and AH/Dogiel type II neurons.

No abstract

The autonomic nervous system is involved in the regulation of visceral function, including the regulation of digestive tract motility. One characteristic of this system is that the nervous regulatory structures are not localized exclusively in the cerebrospinal axis. From a classic point of view, it could be described as having an intrinsic level of regulation located in the viscera and an extrinsic level of regulation in the prevertebral ganglia and central nervous structures, with each level of regulation having its own integrative properties. The prevertebral ganglia, which are part of the sympathetic system, have long been considered as a simple relay on the efferent central pathway. During the last 20 years, numerous studies devoted to the prevertebral ganglia have shown that they behave as true integrative nervous structures able to organize intra-and interorgan regulation.Experiments performed on in vitro preparations consisting of prevertebral ganglia connected to part of the digestive tract have revealed the involvement of these ganglia in the organization of gastrointestinal reflexes. Kreulen & Szurszewski (1979) showed that an inhibitory reflex occurred between two segments of the colon connected only via the coeliac ganglion and the inferior mesenteric ganglion by the mesenteric nerves. This reflex disappeared after sectioning of the intermesenteric nerves. Inhibitory gastrointestinal reflexes organized by the coeliac plexus have also been demonstrated in in vitro models consisting of isolated stomach and duodenum connected only to the coeliac plexus by nervous rami (Kreulen et al. 1983;Mazet et al. 1993b). In a previous study (Mazet et al. 1993b), we demonstrated that a delayed and long-lasting gastrointestinal inhibitory reflex was organized by the coeliac plexus. This nervous Journal of Physiology (1999) 1. The coeliac plexus can organize a gastroduodenal inhibitory reflex without action potentials. The involvement of the nitric oxide-cGMP pathway in this reflex was investigated in the rabbit on an in vitro preparation of the coeliac plexus connected to the stomach and duodenum. Intraluminal duodenal pressures were measured with water-filled balloons. Gastric distension inhibited duodenal motility, thus characterizing a gastroduodenal inhibitory reflex organized by the coeliac plexus. 2. ¬_Arginine, superfused at the coeliac plexus level, enhanced this reflex, whereas N ù -nitro¬_arginine (¬-NOARG) or 2-(4-carboxyphenyl)-4,4,5,5tetramethylimidazoline-1-oxyl-3-oxide (carboxyPTIO) reduced or abolished it. Moreover, diethylamineÏnitric oxide complex superfused at the coeliac plexus level inhibited duodenal motility in the absence of gastric distension. 3. The effects of nitric oxide were mediated through the activation of guanylyl cyclase, as 1H_[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced or abolished the gastroduodenal inhibitory reflex, whereas zaprinast enhanced it. Moreover, 8-bromo-cGMP and cGMP, superfused at the coeliac plexus level, inhibited duodenal motility in the absence of gas...

Trefoil factors (TFFs) are bioactive peptides expressed by several epithelia, including the intestine, where they regulate key functions such as tissue regeneration, barrier function and inflammation. Although food-associated mycotoxins, including deoxynivalenol (DON), are known to impact many intestinal functions, modulation of TFFs during mycotoxicosis has never been investigated. Here, we analyzed the effect of DON on TFFs expression using both human goblet cells (HT29-16E cells) and porcine intestinal explants. Results showed that very low doses of DON (nanomolar range) inhibit the secretion of TFFs by human goblet cells (IC 50 of 361, 387 and 243 nM for TFF1, 2 and 3, respectively) and prevent wound healing. RT-qPCR analysis demonstrated that the inhibitory effect of DON is related to a suppression of TFFs mRNA expression. Experiments conducted on porcine intestinal explants confirmed the results obtained on cells. Finally, the use of specific inhibitors of signal pathways demonstrated that DON-mediated suppression of TFFs expression mainly involved Protein Kinase R and the MAP kinases (MAPK) p38 and ERK1/2. Taken together, our results show for the first time that at very low doses, DON suppresses the expression and production of intestinal TFFs and alters wound healing. Given the critical role of TFFs in tissue repair, our results suggest that DON-mediated suppression of TFFs contributes to the alterations of intestinal integrity the caused by this toxin.