Gastrointestinal tract serotonin

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... 

Atropine and scopolamine have antispasmodic effects on the gastrointestinal tract. It partly inhibits vagal influence in the gut, reducing motility. However, the enteric nervous system also employs serotonin and dopamine, so parasympathetic innervation plays a modulatory role. 

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. 

Ondansetron is a 5HT3 antagonist, blocking serotonin receptors in the central nervous system and the gastrointestinal tract. It is useful in the management of postoperative nausea and vomiting associated with cytotoxics. 

Serotonin (5-hydroxytryptamine, or 5HT) is present in the brain as well as in the periphery. In humans, about 90% of the total serotonin in the body is in enterochro-maffin cells in the gastrointestinal tract the remaining 10% occurs primarily in the platelets and brain. The physiological significance of the vast amounts of serotonin constantly synthesized and metabolized in the periphery still remains an enigma. Brain serotonin has been implicated as a potential neurotransmitter in the mediation of a wide variety of phenomena (see Actions). 

Dietary tryptophan is the source of the formation of serotonin. Enzymes and cofactors necessary for serotonin synthesis are present in both the enterochromaf-lin cells of the gastrointestinal tract and neurons in the brain. Tryptophan is initially hydroxylated to form 5-hydroxytryptophan. Decarboxylation of the latter compound results in the formation of serotonin (Fig. 24.2). 

C. Carcinoid tumors arise from neuroendocrine cells of the gut and secrete serotonin and gastrointestinal hormones, which activate the gastrointestinal tract and result in diarrhea. Most of these tumors have receptors for somatostatin, which inhibit secretion when activated, resulting in reduced activity of the gut. Octreotide is a stable analogue of... 

Nausea is a common early side effect of all SSRIs. Early nausea is probably attributable to the stimulation of serotonin type 3 (5-HT3) receptors in the gastrointestinal tract, which downregulate after several weeks of treatment. Hence this side effect is both dose dependent and transient. Some patients report less nausea if they take the medication with food. Although rarely needed, medication that blocks the 5-HT3 receptor (e.g., ondansetron) can be used to reduce SSRI-induced nausea. 

Dalton SO, Johansen C, Mellemkjaer L, et al Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding a population-based cohort study. Arch Intern Med 163 59-64, 2003... 

Brain serotonergic neurons are involved in numerous diffuse functions such as mood, sleep, appetite, and temperature regulation, as well as the perception of pain, the regulation of blood pressure, and vomiting (see Chapter 21). Serotonin also appears to be involved in clinical conditions such as depression, anxiety, and migraine. Serotonergic neurons are also found in the enteric nervous system of the gastrointestinal tract and around blood vessels. In rodents (but not in humans), serotonin is found in mast cells. 

Serotonin causes blood platelets to aggregate by activating 5-HT2 receptors. This response, in contrast to aggregation induced during clot formation, is not accompanied by the release of serotonin stored in the platelets. The physiologic role of this effect is unclear. Gastrointestinal Tract... 

In most patients, the ergot alkaloids have little or no significant effect on bronchiolar or urinary smooth muscle. The gastrointestinal tract, on the other hand, is quite sensitive. Nausea, vomiting, and diarrhea may be induced even by low doses in some patients. The effect is consistent with action on the central nervous system emetic center and on gastrointestinal serotonin receptors. 

Stimulation of serotonin 3 receptors in the hypothalamus or brainstem may cause nausea or vomiting, respectively (Fig. 5—58). Stimulation of serotonin 3 and 4 receptors in the gastrointestinal tract may cause increased bowel motility, gastrointestinal cramps and diarrhea (Fig. 5—59). 

Ondansetron antagonizes the action of serotonin at receptors in the upper gastrointestinal tract and in the chemoreceptor trigger zone of the central nervous system. Given intravenously (IV), it prevents vomiting completely for 24 h in 40% of patients treated with high doses (>100 mg/m2) of cisplatin and in 70 to 80% of patients treated with 50 to 100 mg/m2 of cisplatin or a combination of cyclophosphamide and doxorubicin. 

Serotonin (5-hydroxytryptamine [5-HT]) produces its effects through a variety of membrane-bound receptors, located in the central and peripheral nervous systems and in non-neuronal tissues in the gastrointestinal tract, cardiovascular system, and blood. The knowledge of the anatomical localization of the receptors is an important step forward for the understanding of their function. Several techniques allow the microscopic visualization of the sites of expression of these receptors in the tissues. In this review, we will attempt to summarize the available information on the neuroanatomical organization of each one of the 5-HT receptor subtypes. 

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