Differential signal pathway activation and 5-HT function: the role of gut enterochromaffin cells as oxygen sensors

Haugen, Martin; Dammen, Rikard; Svejda, Bernhard; Gustafsson, Björn; Pfragner, Roswitha; Modlin, Irvin M.; Kidd, Mark

doi:10.1152/ajpgi.00027.2012

Cited by 23 publications

(22 citation statements)

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“…Other potential sources of elevated serum 5-HT include enterochromaffin (EC) cells of the gut and pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEBs) of the lung. Greater than 90% of the peripheral 5-HT is produced in the gut EC cells, and these cells are known to increase their secretion of 5-HT under various conditions, including hypoxia (35) and infection (36). PNEC and NEBs cells of the lung function as airway oxygen/carbon dioxide sensors and release 5-HT in a dosedependent manner in response to hypoxia (37,38).…”

Section: Discussionmentioning

confidence: 99%

High serum serotonin in sudden infant death syndrome

Haynes

Frelinger

Giles

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality, likely comprises heterogeneous disorders with the common phenotype of sudden death without explanation upon postmortem investigation. Previously, we reported that ∼40% of SIDS deaths are associated with abnormalities in serotonin (5-hydroxytryptamine, 5-HT) in regions of the brainstem critical in homeostatic regulation. Here we tested the hypothesis that SIDS is associated with an alteration in serum 5-HT levels. Serum 5-HT, adjusted for postconceptional age, was significantly elevated (95%) in SIDS infants (n = 61) compared with autopsied controls (n = 15) [SIDS, 177.2 ± 15.1 (mean ± SE) ng/mL versus controls, 91.1 ± 30.6 ng/mL] (P = 0.014), as determined by ELISA. This increase was validated using high-performance liquid chromatography. Thirty-one percent (19/61) of SIDS cases had 5-HT levels greater than 2 SDs above the mean of the controls, thus defining a subset of SIDS cases with elevated 5-HT. There was no association between genotypes of the serotonin transporter promoter region polymorphism and serum 5-HT level. This study demonstrates that SIDS is associated with peripheral abnormalities in the 5-HT pathway. High serum 5-HT may serve as a potential forensic biomarker in autopsied infants with SIDS with serotonergic defects.asphyxia | brainstem | pulmonary neuroepithelial bodies | platelets | high-performance liquid chromatography

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Section: Discussionmentioning

confidence: 99%

High serum serotonin in sudden infant death syndrome

Haynes

Frelinger

Giles

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…124 Responses are augmented by inflammation. Hypoxia stimulates release of adenosine 125,126 and it also acts to stabilize HIF-1α.…”

Section: 0 Adenosinergic Drugsmentioning

confidence: 99%

Potential for Developing Purinergic Drugs for Gastrointestinal Diseases

Ochoa-Cortés¹,

Liñán-Rico²,

Jacobson³

et al. 2014

Inflammatory Bowel Diseases

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Treatments for IBD, IBS, FD or motility disorders are not adequate, and purinergic drugs offer exciting new possibilities. GI symptoms that could be targeted for therapy include visceral pain, inflammatory pain, dysmotility, constipation and diarrhea. The focus of this review is on potential for developing purinergic drugs for clinical trials to treat GI symptoms. Purinergic receptors are divided into adenosine P1 (A1,A2A,A2B,A3), ionotropic ATP-gated P2X ion channel (P2X1–7) or metabotropic P2Y1,2,4,6,11–14 receptors. There is good experimental evidence for targeting A2A, A2B, A3, P2X7, P2X3 receptors or increasing endogenous adenosine levels to treat IBD, inflammatory pain, IBS/visceral pain, inflammatory-diarrhea and motility disorders. Purine genes are also potential biomarkers of disease. Advances in medicinal-chemistry have an accelerated pace toward clinical trials: Methotrexate and sulfasalazine, used to treat IBD, act by stimulating CD73-dependent adenosine production. ATP protects against NSAID-induced enteropathy and has pain-relieving properties in humans. A P2X7R antagonist AZD9056 is in clinical trials for CD. A3 AR drugs target inflammatory diseases (e.g. CF101; CF102). Dipyridamole, a nucleoside uptake-inhibitor, is in trials for endotoxemia. Drugs for pain in clinical-trials include P2X3/P2X2/3(AF-219) and P2X7(GSK1482160) antagonists and A1(GW493838) or A2A(BVT.115959) agonists. IberogastR is a phytopharmacon targeting purine-mechanisms with efficacy in IBS and FD. Purinergic drugs have excellent safety/efficacy profile for prospective clinical trials in IBD, IBS, FD and inflammatory-diarrhea. Genetic polymorphisms and caffeine consumption may affect susceptibility to treatment. Further studies in animals can clarify mechanisms and test new-generation drugs. Finally, there is still a huge gap in our knowledge of human pathophysiology of purinergic signaling.

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“…Eradication of H. pylori infection has helpful outcomes to improve clinical attacks [14][15][16][17]. This was attributed to the effect of eradication therapy on the inflammation induced high levels of 5-HT [17,18].…”

Section: Open Accessmentioning

confidence: 99%