Enterochromaffin cell

Carboline derivatives in various oxidation states have been isolated from a number of natural sources as artifacts. )3-Carboline has been obtained from charred insects, j8-carboline and l-methyl-)3-carboline have been found in cigarette smoke,and the formation of tetrahydro-j8-carboline derivatives has been shown to be responsible for the destruction of tryptophan in acid hydrolyzates of proteins. The golden-yeUow fluorescence observed when enterochromaffin cells are flxed in formaldehyde has been related to their content of... 

The neurokinin, substance P (SP), may be involved as a sensory transmitter in afferent vagal nerves involved in the vomiting reflex. Both SP and its receptors (NKi receptors) have been detected in several areas of the brain associated with vomiting, including the AP, NTS and dorsal motor vagal nucleus. The neurokinin can activate neurons in the AP and NTS. SP is present also in sensory nerves in the gut as well as being co-localised with serotonin in some enterochromaffin cells. 

Cytotoxics also cause cellular damage and the release of serotonin and other mediators from enterochromaffin cells. There is conflicting evidence regarding whether 5-HT3 receptors in the medulla are activated also during chemotherapy and contribute to production of emesis. Currently, the weight of evidence favours peripheral 5-HT3 receptors, with minor involvement of central receptors. 

Motilin is a 22-amino acid peptide hormone, secreted by the enterochromaffin cells of the small intestine,... 

Enterochromaffin cells are interspersed with mucosal cells mainly in the stomach and small intestine. In the blood, serotonin is present at high concentrations in platelets, which take up serotonin from the plasma by an active transport process. Serotonin is released on platelet activation. In the central nervous system, serotonin serves as a transmitter. The main serotonin-containing neurons are those clustered in form of the Raphe nuclei. Serotonin exerts its biological effects through the activation of specific receptors. Most of them are G-protein coupled receptors (GPCRs) and belong to the 5-HTr, 5-HT2-, 5-HT4-, 5-HTs-, 5-HT6-, 5-HT7-receptor subfamilies. The 5-HT3-receptor is a ligand-operated ion channel. 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Serotonin is synthesized from tryptophan in two steps. Tryptophan is hydroxylated by tryptophan hydroxylase, and 5-hydroxytryptophan is decarboxylated to give serotonin. Most serotonin in the body is found in the enterochromaffin cells of the intestinal tract and the pineal gland. Platelets take up and store serotonin but do not synthesize it. 

Over 95% of the body s serotonin (5-HT) is found in the gastrointestinal tract in enterochromaffin cells and neurons. There are 18 known serotonin receptor sub-types, of which 5-HT, 5-HT3, and 5-HT are located in the gut and modulate gut secretion, motility, and sensation (57). The 5-HT in the synaptic spaces stimulates these receptors until it is actively cleared by a 5-HT transporter protein located on the presynaptic neuronal endings. 

Gastric secretion. Stimulation of gastric acid production by vagal impulses involves an M-cholinoceptor subtype (M -receptor), probably associated with enterochromaffin cells. Pirenzepine (p. 106) displays a preferential affinity for this receptor subtype. Remarkably, the HCl-secreting parietal cells possess only Ma-receptors. Mi-receptors have also been demonstrated in the brain however, these cannot be reached by pirenzepine because its lipophilicity is too low to permit penetration of the blood-brain barrier. Pirenzepine was formerly used in the treatment of gastric and duodenal ulcers (p. 166). 

Occurrence. Serotonin (5-hydroxytrypt-amine, 5-HT) is synthesized from L-tryptophan in enterochromaffin cells of the intestinal mucosa 5-HT-synthesiz-ing neurons occur in the enteric nerve plexus and the OIS, where the amine fulfills a neuromediator functioa Blood platelets are unable to synthesize 5HT, but are capable of taking up, storing, and releasing it... 

Gastrointestinal tract. Serotonin released from myenteric neurons or enterochromaffin cells acts on 5-HT3 and 5-HT4 receptors to enhance bowel motility and enteral fluid secretion Cisapride is a proldnetic agent that promotes propulsive motor activity in the stomach and in small and large intestines. It is used in motility disorders. Its mechanism of action is unclear, but stimulation of 5HT4 receptors may be important... 

In the mucosa of the gastrointestinal tract histamine is present in enterochromaffin cells. These cells are thought to contain the histamine which is involved in the stimulation of gastric acid secretion. In the central nervous system there are histaminergic neurons. 

Hydroxytryptamine is widely distributed in plant and animal tissues, mast cells, platelets, the enterochromaffin cells located throughout the gastrointestinal tract, and in certain regions of the brain. It is also present in the venoms and stings. Some fruits such as bananas, pineapples, tomatoes and plums contain considerable amount of 5-HT. 

A highly simplified diagram of the intestinal wall and some of the circuitry of the enteric nervous system (ENS). The ENS receives input from both the sympathetic and the parasympathetic systems and sends afferent impulses to sympathetic ganglia and to the central nervous system. Many transmitter or neuromodulator substances have been identified in the ENS see Table 6-1. ACh, acetylcholine AC, absorptive cell CM, circular muscle layer EC, enterochromaffin cell EN, excitatory neuron EPAN, extrinsic primary afferent neuron 5HT, serotonin IN, inhibitory neuron IPAN, intrinsic primary afferent neuron LM, longitudinal muscle layer MP, myenteric plexus NE, norepinephrine NP, neuropeptides SC, secretory cell SMP, submucosal plexus. 

Serotonin is an important neurotransmitter, a local hormone in the gut, a component of the platelet clotting process, and is thought to play a role in migraine headache. Serotonin is also one of the mediators of the signs and symptoms of carcinoid syndrome, an unusual manifestation of carcinoid tumor, a neoplasm of enterochromaffin cells. In patients whose tumor is not operable, a serotonin antagonist may constitute a useful treatment. 

The function of serotonin in enterochromaffin cells is not fully understood. These cells synthesize serotonin, store the amine in a complex with ATP and with other substances in granules, and release serotonin in response to mechanical and neuronal stimuli. This paracrine serotonin interacts with several 5-HT receptors in the gut. Some of the released serotonin diffuses into blood vessels and is taken up and stored in platelets. 

Schworer H, Reimann A, Ramadori G, Racke K (1994) Characterization of histamine H3 receptors inhibiting 5-HT release from porcine enterochromaffin cells further evidence for H3 receptor heterogeneity. Naunyn-Schmiedeberg s Arch... 

Histamine H3 receptors were also found to occur in porcine small intestine where they inhibit the release of 5-hydroxytryptamine from enterochromaffin cells (Schworer et al., 1992). 

McKay, D.M., Halton, D.W., Johnston, C.F., Fairweather, I. and Shaw, C. (1990a) EJymenolepis diminuta changes in intestinal morphology and the enterochromaffin cell population associated with infection in male C57 mice. Parasitology 1 01, 1 07-11 3. 

VMAT1 Endocrine tissue Sympathetic ganglia Enterochromaffin cells Monoamines (Km low pM range) Monoamine analogues Toxins (e.g. MPP+) Reserpine (Ki 34 nM) Psychostimulantia (e.g. Amphetamine, cocaine)... 

The main source of serotonin (5-HT) is the enterochromaffin cells, which release it as tissue hormone either into the gut lumen or the portal vein circulation. In the CNS, cell bodies of 5-HT-containing neurons are concentrated along the raphe nuclei of the brainstem and are also found in more lateral regions and in the reticular formation. The neurons terminate in almost all brain regions and in the spinal cord. 

Carcinoid is a tumor of the enterochromaffin cells that normally synthesize 5-hydroxytrytophan and 5-hydroxytryptamine. The carcinoid syndrome is seen when there are significant metastases of the primary tumor in the liver. It is characterized by increased gastrointestinal motility and diarrhea, as well as by regular periodic flushing. These symptoms can be attributed to systemic release of large amounts of serotonin and can be controlled with inhibitors of tryptophan hydroxylase, such as p-chlorophenylalanine. The synthesis of 5-hydroxytryptamine in advanced carcinoid syndrome may be so great that as much as 60% of the body s tryptophan metabolism proceeds by this pathway, compared with about 1% under normal conditions. A significant number of... 

Serotonin (5-hydroxytryptamine, 5-HT) is synthesised in enterochromaffin cells, largely in the gut, and also extensively taken up into blood platelets from which it is released to have vascular effects. It has complex effects on the cardiovascular system, varying with the vascular bed and its physiological state it generally constricts arterioles and veins and induces blood platelet aggregation it stimulates intestinal and bronchial smooth muscle. Carcinoid tumours secrete serotonin and symptoms may be benefited by serotonin antagonists, e.g. cyproheptadine, methysergide and sometimes by octreotide (see Index). It is a neurotransmitter in the brain. 

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