Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, in most patients, tumor growth is rather slow, and even in advanced metastatic disease, there is very little impairment of the general well-being of the individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptide hormones which may be factors in some clinical conditions e.g. carcinoid, Zollinger-Ellison and hypoglycemic syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrine tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always in parallel. Systemic treatment of neuroendocrine tumors mainly consists of chemotherapy, interferon and somatostatin analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocin with 5-fluorouracil or adriamycin. This combination produces biochemical responses in up to 60% of patients with endocrine pancreatic tumors; the results in carcinoid patients are very poor and response rates are < or = 10%. Alpha-interferon (IFN-alpha) produces biochemical responses in approximately 50% of patients with malignant carcinoid tumors, significant reductions in tumor size in 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatin analogs have only been used clinically within the last 10 years, but produce symptomatic improvement in 70% of cases, biochemical responses in 40-60%, but rarely produce any significant reduction in tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carcinoid patients both peri- and intra-operatively. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasointestinal peptide-producing tumors, benefit most from this type of treatment. Recently, a combination of IFN-alpha and a somatostatin analog has showed an additive effect of these two drugs. The side effects of streptozotocin and 5-fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction is impaired renal function. The adverse reactions to IFN-alpha are mainly flu-like symptoms, fatigue, mild impairment of liver and bone marrow function and autoimmune reactions in 15% cases. Somatostatin analog treatment causes a low frequency of adverse reactions, those which do occur include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Endocrine tumors of the gastrointestinal tract: systemic treatment. 785 82

Effects of tryptamine on tolbutamide-induced hypoglycemia were investigated in mice. Tryptamine significantly inhibited hypoglycemia elicited by tolbutamide. The inhibitory effects of tryptamine were strongly blocked by the 5-HT1 and 5-HT2 receptor antagonist methysergide and the 5-HT2 receptor antagonist ketanserin, while the 5-HT3 receptor antagonist ICS 205-930 was without effect. Tryptamine induced hyperglucagonemia in tolbutamide-treated mice, and this effect elicited by tryptamine was strongly inhibited by the 5-HT2 receptor antagonist ketanserin. These results suggest that the inhibitory effects of tryptamine on tolbutamide-induced hypoglycemia are mediated by 5-HT2 receptors and that tryptamine is involved in glucagon release.
 ...
PMID:Inhibitory effects of tryptamine on tolbutamide-induced hypoglycemia in mice: mediation by 5-HT receptors. 813 57

Peripherally administered serotonin (5-HT) induced a marked increase in the plasma glucagon level in mice. The hyperglucagonemic effects of 5-HT were completely antagonized by methysergide, ketanserin and ritanserin which have a high affinity for 5-HT2 receptors. However, the 5-HT3 receptor antagonist ICS 205-930 and MDL 72222 were without effect. These findings suggest that the activation of the peripheral 5-HT2 receptor induces the increase in plasma glucagon level and that these receptors may play a role in the release of glucagon.
 ...
PMID:Peripherally administered serotonin induces hyperglucagonemia in mice. 850 21

The involvement of the peripheral serotonin2A (5-HT2A) receptor in alpha-methyl-5-HT-induced hyperglycemia was examined in rats. The 5-HT2A receptor antagonist, ketanserin, significantly inhibited alpha-methyl-5-HT-elicited hyperglycemia. Taken together with a previous report that 5-HT-induced hyperglycemia was prevented by ketanserin, it is suggested that the peripheral 5-HT2A receptor participates in glucose regulation. As alpha-methyl-5-HT increased serum insulin but did not affect glucagon levels, it is indicated that these pancreatic hormones are probably not related to alpha-methyl-5-HT-induced hyperglycemia. Moreover, the peripheral 5-HT3 receptor agonist, 2-methyl-5-HT, did not affect blood glucose, insulin or glucagon levels. Our results therefore suggest that the peripheral 5-HT3 receptor is not involved in glucose regulation.
 ...
PMID:The effects of peripheral serotonin2 (5-HT2) and serotonin3 (5-HT3) receptor agonists on blood glucose levels in rats. 891 20

Glucagon-like peptide-1 (GLP-1) is an incretin hormone with a number of functions to maintain energy homeostasis and contribute to motivated behavior, both peripherally and within the central nervous system (CNS). These functions, which include insulin secretion, gastric emptying, satiety, and the hedonic aspects of food and drug intake, are primarily mediated through stimulation of the GLP-1 receptor. While this receptor plays an important role in a variety of physiological outcomes, data regarding its CNS expression has been primarily limited to regional receptor binding and single-label transcript expression studies. We thus developed a bacterial artificial chromosome transgenic mouse, in which expression of a red fluorescent protein (mApple) is driven by the GLP-1R promoter. Using this reporter mouse, we characterized the regional and cellular expression patterns of GLP-1R expressing cells in the CNS, using double-label immunohistochemistry and in situ hybridization. GLP-1R-expressing cells were enriched in several key brain regions and circuits, including the lateral septum, hypothalamus, amygdala, bed nucleus of the stria terminalis, hippocampus, ventral midbrain, periaqueductal gray, and cerebral cortex. In most regions, GLP-1R primarily colocalized with GABAergic neurons, except within some regions such as the hippocampus, where it was co-expressed in glutamatergic neurons. GLP-1R-mApple cells were highly co-expressed with 5-HT3 receptor-containing neurons within the cortex and striatum, as well as with dopamine receptor- and calbindin-expressing cells within the lateral septum, the brain region in which GLP-1R is most highly expressed. In this manuscript, we provide detailed images of GLP-1R-mApple expression and distribution within the brain and characterization of these neurons.
 ...
PMID:A novel mouse model of glucagon-like peptide-1 receptor expression: A look at the brain. 3217 Jul 34

Irritable bowel syndrome (IBS) is one of the most commonly diagnosed functional gastrointestinal (GI) disorders. It affects both men and women. Enteric serotonin (5HT) is responsible for gut motility, secretion, visceral hypersensitivity, and inflammation. The serotonin reuptake transporter (SERT) maintains serotonin levels by regulating its reuptake. An increase in SERT expression causes a decrease in serotonin, which leads to IBS-C (irritable bowel syndrome, constipation-predominant), whereas a decrease in SERT transcription causes an increase in serotonin, which leads to IBS-D (irritable bowel syndrome, diarrhea-predominant). Some factors can alter SERT transcription, such as certain bacteria, inflammation, growth factor, and glucagon-like peptide-1. This shows that 5HT and SERT both have an important role in IBS pathophysiology so that it would be a better subject to target for the treatment aspect of IBS. 5HT3 receptor antagonists are advisable for IBS-D to block the excessive activity of serotonin at the 5HT3 receptor and reduce gut motility. For IBS-C, we prescribe 5HT4 receptor agonists, which promote gut motility. Also, the latest treatment approach, antidepressant drugs TCAs (tricyclic antidepressants) and SSRIs (selective serotonin reuptake inhibitors), are helpful by modulating serotonin levels in the gut. In this literature review, we found that serotonin is one of the main pathophysiological factors for IBS, and we can treat IBS by targeting serotonin function on gut motility.
 ...
PMID:How Serotonin Level Fluctuation Affects the Effectiveness of Treatment in Irritable Bowel Syndrome. 3296 14