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The intestinal blood flow is also controlled by extrinsic and intrinsic neurones. Vessels are innervated by both vasoconstrictor and vasodilator fibres, considered sympathetic and parasympathetic, respectively fig.

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On the other hand, the myenteric and submucous nerve plexuses have continuous capillary networks, which functionally connect them. Submucous neurones are the primary vasomotor effectors and excitation of these neurones leads to vasodilatation and therefore increased flow to the mucosa Hansen et al. Under resting conditions, mucosal perfusion is mainly regulated by the vasodilators, nitric oxide and prostaglandin I2, and the vasoconstrictors, endothelin, norepinephrine, adenosine triphosphate, and neuropeptide Y fig.

The effect of extrinsic stimuli on the enteric nervous system and arteriolar smooth muscle cell. Local production of vasoactive mediators by adjacent neurones, endothelial cells, platelets, and other vascular smooth muscle cells in response to stimuli hypoxia, chyme, etc.

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Reproduced from Hansen et al. The sympathetic nervous influence of the microcirculation overshadows that of the other determinants. But activation of additional receptors can either facilitate e. Norepinephrine causes redistribution of the flow to and within the mucosa, with increased flow to the villi hyperaemia and decreased flow to the crypts. This flow change does not alter the absorption rate in the villi, but reduces the secretion rate in the crypts.

Whereas direct application of acetylcholine on vascular smooth muscle causes vasoconstriction, release of acetylcholine by neurones is generally associated with vasodilatation. The muscarinic receptors are located on the endothelium and activation leads to the release of nitric oxide from endothelial cells. Nitric oxide appears to be a major determinant of vascular tone in mesenteric resistance vessels and submucous arterioles. Nitric oxide diffuses to the vascular smooth muscle and causes relaxation and vasodilatation.

Nearly all vasodilator neurones are immunoreactive to vasoactive intestinal polypeptide, which suggests that vasoactive intestinal peptide may be a mediator to acetylcholine in the parasympathetic relaxation mechanism Ekblad et al. The afferent nerves, which serve as luminal sensors, regulate local blood flow by releasing neuroendocrine substances.

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

They are type C fibres and are sensitive to capsaicin and lidocaine. These nerves are activated by mechanical, thermal stimuli, ischaemia, and hypoxia and bring about an increased local blood flow. This reflex vasodilatation appears to be the result of activation of inhibitory synaptic nerves from sympathetic and myenteric ganglia and synaptic activity in submucous neurones containing vasoactive intestinal peptide.

These substances stimulate the submucous nerve plexus and cause vasodilatation of submucous arterioles.


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The enteric nervous system plays a pathogenic role for the vascular alterations found in a number of diseases, including hypertension, diabetes mellitus, hypothyroidism, angiodysplasia, tumours, radiation sequelae, intestinal angina, and bowel necrosis Hansen et al. The immune system and enteric nervous system are powerful defenders of the body's enteric frontiers. To stress the strong interaction between the enteric nervous system and the immune system, receptors for enteric neurotransmitters are located on the Peyer's patches and lymphocytes located in the lamina propria.

Motor and secretory responses are sensitised to specific antigens e. Intestinal inflammation is associated with disturbed whole gut motility and enteric nervous system function. For example in enteritis caused by Clostridium difficile toxin A, enteric neurones are excited and the sympathetic neurotransmission is suppressed.

The immune system and its messengers, the inflammatory mediators, sensitise primary afferents, especially the C fibre nociceptors, favouring the recruitment of silent nociceptors, which give rise to secondary spinal activation. This is termed neurogenic inflammation. An important example is the mast cells. These substances activate specific receptors on vagal afferents. The enteric nervous system interprets the mast cell signal as a threat and calls up from its programme library secretory and propulsive motor behaviour organised for quick and effective eradication of the threat.

In some patients with irritable bowel syndrome, the average number of immune and inflammatory cells in the colonic mucosa is increased in close vicinity to the nerve trunks.

Axon Regeneration in the CNS: Insights from the Optic Nerve

Hypoganglionosis is not only confined to the myenteric plexus but also to the submucous plexus in chronic intestinal pseudoobstruction Von Boyen et al. In different infectious states e. These infections seem to activate the immune system to assault neurones coincident with the attack on the parasites Smith et al.

Neurogenic inflammation is reduced by some of the receptor antagonists e. Novel classes of receptors involved in neurogenic inflammation are evolving. Several neuroendocrine substances e. In the gastric and small intestinal wall, chemoreceptors are activated and release these substances e. Cholecystokinin stimulates CCK 1 receptors on vagal afferents in the process of controlling gastric emptying. CCK 1 receptor antagonists stimulate appetite, inhibit release of pancreatic enzymes and gall bladder contraction and increase food intake.

Gall bladder and Oddi's sphincter responses with active contraction and relaxation are produced by neural and local control elements. However, the vagus nerve provides the major input Muramatsu et al. The cholinergic efferent vagal projections terminate in the gall bladder ganglia, where they activate cells through cholinergic muscarinic and nicotinic receptors. Sympathetic nerve fibres originate in the celiac ganglion Mawe et al.

A preserved extrinsic neural connection between gall bladder and residual stomach is essential to prevent dysmotility of the gallbladder as demonstrated after experimental gastrectomy in dogs Tsukamoto et al. The ganglionic layer of the gall bladder and the Oddi's sphincter is distinct from that of the intestines. It resembles the submucous plexus.

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Pathophysiologically, cholelithiasis is still regarded as a state of dysmotility of the gallbladder. The postcholecystectomy syndrome is probably also a condition of dysmotility of the Oddi's sphincter as abnormal higher pressure is often present in the central duct system. Dysfunction of Oddi's sphincter could be the outcome of loss of myenteric inhibitory neurones resulting in opposing cholinergic tone. The somatostatin analogue, octreotide, and the synthetic prostaglandin E 1 analogue, alprostadil alfadex, reduce the pressure of Oddi's sphincter and might be valuable in the management of the postcholecystectomy syndrome Fazel et al.

The pancreatic endocrine and exocrine function is also regulated by numerous neuroendocrine substances e. As for the rest of the enteric nervous system, the pancreatic intrinsic nervous system interacts with extrinsic innervation from the central nervous system Berthoud et al.

Secretin is released by gastric acid from S cells in the proximal small intestine and stimulates vagal afferents Holzer It is the most important stimulus to pancreatic secretion of fluid and electrolytes in the fasting state. However mediation of postprandial pancreatic enzyme secretion is ascribed mainly to cholecystokinin and to vagovagal reflexes that activate cholinergic postganglionic neurones in the pancreas. In states of acute and chronic pancreatitis, where pathophysiological mechanisms include pancreatic inflammation, neural alterations and intraductal hypertension, these agents might be of special benefit Salvioli et al.

The importance of the enteric nervous system for gastrointestinal functions in health and disease is now emerging. But we still have quite a way to go before we have a complete picture of the pathophysiological role of enteric nervous system. Subjects with enteric neuropathy, such as functional gastrointestinal disorders, are now relevant targets for further experimental and clinical studies.


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Lastly, further development of easily applicable and reliable technologies for in vivo studies in man is needed in order to assess the importance of enteric nervous system for gut functions. Volume 92 , Issue 6. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account. If the address matches an existing account you will receive an email with instructions to retrieve your username.

Free Access. Tools Request permission Export citation Add to favorites Track citation. Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article. Abstract Abstract: The enteric nervous system is involved in most of the physiological and pathophysiological processes in the gastrointestinal tract. Figure 1 Open in figure viewer PowerPoint.

About this product. Stock photo. Brand new: lowest price The lowest-priced brand-new, unused, unopened, undamaged item in its original packaging where packaging is applicable. Title Nitric Oxide in the Nervous System. Author Tom Vincent. Format Hardcover. Edition 1st. See details. Buy It Now. Add to cart. Be the first to write a review About this product.

The Enteric Nervous System II: Gastrointestinal Functions

About this product Product Information It is hoped that this volume will provide a synopsis of what we now know about nitric oxide. How and where nitric oxide is produced, how it acts at the molecular level to activate the synthesis of cGMP, and the possible targets of cGMP in the nervous system are reviewed. Additional Product Features Dewey Edition. Koesling, P. Humbert, and G. Amir, Nitric Oxide Signaling in the Hypothalamus. Murphy, D. Grzybicki, and M. Varner and J. Rand and C.