Non-conventional features of peripheral serotonin signalling-the gut and beyond

Nature Reviews Gastroenterology and Hepatology

Volumn 14, Issue 7, 2017, Pages 412-420

  Spohn, Stephanie N ^a,b   Mawe, Gary M ^a  

^a UNIVERSITY OF VERMONT   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 HYDROXYINDOLEACETIC ACID; SEROTONIN; SEROTONIN 4 RECEPTOR; SEROTONIN 7 RECEPTOR; SEROTONIN TRANSPORTER; SEROTONIN UPTAKE INHIBITOR; SHORT CHAIN FATTY ACID; TRYPTOPHAN HYDROXYLASE; AUTACOID;

ADIPOSE TISSUE; BONE MASS; BONE METABOLISM; BONE REMODELING; COLITIS; CONSTIPATION; DENDRITIC CELL; DEPRESSION; DIARRHEA; ENERGY METABOLISM; ENTEROCHROMAFFIN CELL; ERYTHROPOIESIS; FRACTURE; GASTROINTESTINAL TRACT; GLUCOSE METABOLISM; HEMATOPOIESIS; HUMAN; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; INTESTINE MUCOSA; LIVER CELL; NAUSEA; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; REVIEW; SEROTONIN RELEASE; SIDE EFFECT; HOMEOSTASIS; INTESTINE INNERVATION; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

BONE REMODELING; COLITIS; ENTERIC NERVOUS SYSTEM; GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL TRACT; HEMATOPOIESIS; HOMEOSTASIS; HUMANS; INFLAMMATION MEDIATORS; SEROTONIN; SIGNAL TRANSDUCTION;

EID: 85019150698     PISSN: 17595045     EISSN: 17595053     Source Type: Journal    
DOI: 10.1038/nrgastro.2017.51     Document Type: Review

References (90)

1. Gershon, M. D. 5 Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr. Opin. Endocrinol. Diabetes Obes. 20, 14-21 (2013).
2. Erspamer, V. Experimental research on the biological significance of enterochromaffin cells [Italian]. Arch. Fisiol. 37, 156-159 (1937).
3. Erspamer, V., & Asero, B. Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5 hydroxytryptamine. Nature 169, 800-801 (1952).
4. Mawe, G. M., & Hoffman, J. M. Serotonin signalling in the gut-functions, dysfunctions and therapeutic targets. Nat. Rev. Gastroenterol. Hepatol. 10, 473-486 (2013).
5. Smith, T. K., & Gershon, M. D. CrossTalk proposal: 5 HT is necessary for peristalsis. J. Physiol. 593, 3225-3227 (2015).
6. Spencer, N. J., Sia, T. C., Brookes, S. J., Costa, M., & Keating, D. J. CrossTalk opposing view: 5 HT is not necessary for peristalsis. J. Physiol. 593, 3229-3231 (2015).
7. Page, I. H., Rapport, M. M., & Green, A. A. The crystallization of serotonin. J. Lab. Clin. Med. 33, 1606 (1948).
8. Rapport, M. M., Green, A. A., & Page, I. H. Partial purification of the vasoconstrictor in beef serum. J. Biol. Chem. 174, 735-741 (1948).
9. Bertaccini, G. Tissue 5 hydroxytryptamine and urinary 5 hydroxyindoleacetic acid after partial or total removal of the gastro-intestinal tract in the rat. J. Physiol. 153, 239-249 (1960).
10. Cote, F., et al. Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc. Natl Acad. Sci. USA 100, 13525-13530 (2003).
11. Walther, D. J., & Bader, M. A unique central tryptophan hydroxylase isoform. Biochem. Pharmacol. 66, 1673-1680 (2003).
12. Kim, H., et al. Serotonin regulates pancreatic beta cell mass during pregnancy. Nat. Med. 16, 804-808 (2010).
13. Paulmann, N., et al. Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation. PLoS Biol. 7, e1000229 (2009).
14. Stunes, A. K., et al. Adipocytes express a functional system for serotonin synthesis, reuptake and receptor activation. Diabetes Obes. Metab. 13, 551-558 (2011).
15. Chabbi-Achengli, Y., et al. Decreased osteoclastogenesis in serotonin-deficient mice. Proc. Natl Acad. Sci. USA 109, 2567-2572 (2012).
16. Neunlist, M., & Schemann, M. Nutrient-induced changes in the phenotype and function of the enteric nervous system. J. Physiol. 592, 2959-2965 (2014).
17. Reigstad, C. S., et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 29, 1395-1403 (2015).
18. Jones, R. M. The influence of the gut microbiota on host physiology: in pursuit of mechanisms. Yale J. Biol. Med. 89, 285-297 (2016).
19. Hurst, N. R., Kendig, D. M., Murthy, K. S., & Grider, J. R. The short chain fatty acids, butyrate and propionate, have differential effects on the motility of the guinea pig colon. Neurogastroenterol. Motil. 26, 1586-1596 (2014).
20. Hoffman, J. M., et al. Activation of colonic mucosal 5 HT4 receptors accelerates propulsive motility and inhibits visceral hypersensitivity. Gastroenterology 142, 844-854.e4 (2012).
21. Wang, F., et al. Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces. J. Physiol. 595, 79-91 (2017).
22. Yano, J. M., et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264-276 (2015).
23. Aherne, C. M., Collins, C. B., & Eltzschig, H. K. Netrin 1 guides inflammatory cell migration to control mucosal immune responses during intestinal inflammation. Tissue Barriers 1, e24957 (2013).
24. Bischoff, S. C., et al. Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2, 4, 6 trinitrobenzene sulfonic acid colitis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G685-G695 (2009).
25. Ghia, J. E., et al. Serotonin has a key role in pathogenesis of experimental colitis. Gastroenterology 137, 1649-1660 (2009).
26. Kim, J. J., et al. Blocking peripheral serotonin synthesis by telotristat etiprate (LX1032/LX1606) reduces severity of both chemical-And infection-induced intestinal inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 309, G455-G465 (2015).
27. Margolis, K. G., et al. Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut 63, 928-937 (2014).
28. Li, N., et al. Serotonin activates dendritic cell function in the context of gut inflammation. Am. J. Pathol. 178, 662-671 (2011).
29. Kim, J. J., et al. Targeted inhibition of serotonin type 7 (5 HT7) receptor function modulates immune responses and reduces the severity of intestinal inflammation. J. Immunol. 190, 4795-4804 (2013).
30. Gershon, M. D. Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense. Trans. Am. Clin. Climatol. Assoc. 123, 268-280 (2012).
31. Motomura, Y., et al. Enterochromaffin cell and 5 hydroxytryptamine responses to the same infectious agent differ in Th1 and Th2 dominant environments. Gut 57, 475-481 (2008).
32. Foley, K. F., Pantano, C., Ciolino, A., & Mawe, G. M. IFN-gamma and TNF-Alpha decrease serotonin transporter function and expression in Caco2 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G779-G784 (2007).
33. Spohn, S. N., et al. Protective actions of epithelial 5 hydroxytryptamine 4 receptors in normal and inflamed colon. Gastroenterology 151, 933-944 (2016).
34. Li, Z., et al. Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J. Neurosci. 31, 8998-9009 (2011).
35. Liu, M. T., Kuan, Y. H., Wang, J., Hen, R., & Gershon, M. D. 5 HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice. J. Neurosci. 29, 9683-9699 (2009).
36. Margolis, K. G., et al. Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function. J. Clin. Invest. 126, 2221-2235 (2016).
37. Bianco, F., et al. Prucalopride exerts neuroprotection in human enteric neurons. Am. J. Physiol. Gastrointest. Liver Physiol. 310, G768-G775 (2016).
38. Belkind-Gerson, J., et al. Colitis induces enteric neurogenesis through a 5 HT4 dependent mechanism. Inflamm. Bowel Dis. 21, 870-878 (2015).
39. Matsuyoshi, H., et al. A 5 HT4-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult. Neurogastroenterol. Motil. 22, 806-e226 (2010).
40. Tharayil, V. S., et al. Lack of serotonin 5 HT2B receptor alters proliferation and network volume of interstitial cells of Cajal in vivo. Neurogastroenterol. Motil. 22, 462-e110 (2010).
41. Lowy, P. H., Keighley, G., & Cohen, N. S. Stimulation by serotonin of erythropoietin-dependent erythropoiesis in mice. Br. J. Haematol. 19, 711-718 (1970).
42. Yang, M., et al. Promoting effects of serotonin on hematopoiesis: ex vivo expansion of cord blood CD34+ stem/progenitor cells, proliferation of bone marrow stromal cells, and antiapoptosis. Stem Cells 25, 1800-1806 (2007).
43. Yang, M., Srikiatkhachorn, A., Anthony, M., & Chong, B. H. Serotonin stimulates megakaryocytopoiesis via the 5 HT2 receptor. Blood Coagul. Fibrinolysis 7, 127-133 (1996).
44. Amireault, P., et al. Serotonin is a key factor for mouse red blood cell survival. PLoS ONE 8, e83010 (2013).
45. Amireault, P., et al. Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice. Proc. Natl Acad. Sci. USA 108, 13141-13146 (2011).
46. Breum, L., Rasmussen, M. H., Hilsted, J., & Fernstrom, J. D. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am. J. Clin. Nutr. 77, 1112-1118 (2003).
47. Kim, H. J., et al. Metabolomic analysis of livers and serum from high-fat diet induced obese mice. J. Proteome Res. 10, 722-731 (2011).
48. Bertrand, R. L., et al. A Western diet increases serotonin availability in rat small intestine. Endocrinology 152, 36-47 (2011).
49. Voigt, J. P., & Fink, H. Serotonin controlling feeding and satiety. Behav. Brain Res. 277, 14-31 (2015).
50. Kim, K., et al. Functional role of serotonin in insulin secretion in a diet-induced insulin-resistant state. Endocrinology 156, 444-452 (2015).
51. Zelkas, L., et al. Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability. Nutr. Metab. (Lond.) 12, 55 (2015).
52. Sumara, G., Sumara, O., Kim, J. K., & Karsenty, G. Gut derived serotonin is a multifunctional determinant to fasting adaptation. Cell Metab. 16, 588-600 (2012).
53. Oh, C. M., et al. Regulation of systemic energy homeostasis by serotonin in adipose tissues. Nat. Commun. 6, 6794 (2015).
54. Crane, J. D., et al. Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nat. Med. 21, 166-172 (2015).
55. Siddiqui, J. A., & Partridge, N. C. Physiological bone remodeling: systemic regulation and growth factor involvement. Physiology (Bethesda) 31, 233-245 (2016).
56. Yadav, V. K., et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138, 976-989 (2009).
57. Gong, Y., et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107, 513-523 (2001).
58. Boyden, L. M., et al. High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med. 346, 1513-1521 (2002).
59. Yadav, V. K., et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135, 825-837 (2008).
60. Kode, A., et al. FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin. J. Clin. Invest. 122, 3490-3503 (2012).
61. Yadav, V. K., et al. Pharmacological inhibition of gut derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat. Med. 16, 308-312 (2010).
62. Blazevic, S., Erjavec, I., Brizic, M., Vukicevic, S., & Hranilovic, D. Molecular background and physiological consequences of altered peripheral serotonin homeostasis in adult rats perinatally treated with tranylcypromine. J. Physiol. Pharmacol. 66, 529-537 (2015).
63. Erjavec, I., et al. Constitutively elevated blood serotonin is associated with bone loss and type 2 diabetes in rats. PLoS ONE 11, e0150102 (2016).
64. Cui, Y., et al. Lrp5 functions in bone to regulate bone mass. Nat. Med. 17, 684-691 (2011).
65. Rizzoli, R., et al. Antidepressant medications and osteoporosis. Bone 51, 606-613 (2012).
66. Mezuk, B., Eaton, W. W., & Golden, S. H. Depression and osteoporosis: epidemiology and potential mediating pathways. Osteoporos Int. 19, 1-12 (2008).
67. Warden, S. J., Robling, A. G., Sanders, M. S., Bliziotes, M. M., & Turner, C. H. Inhibition of the serotonin (5 hydroxytryptamine) transporter reduces bone accrual during growth. Endocrinology 146, 685-693 (2005).
68. Garfield, L. D., et al. Genetic variation in the serotonin transporter and HTR1B receptor predicts reduced bone formation during serotonin reuptake inhibitor treatment in older adults. World J. Biol. Psychiatry 15, 404-410 (2014).
69. Suarez-Trujillo, A., & Casey, T. M. Serotoninergic and circadian systems: driving mammary gland development and function. Front. Physiol. 7, 301 (2016).
70. Durk, T., et al. Production of serotonin by tryptophan hydroxylase 1 and release via platelets contribute to allergic airway inflammation. Am. J. Respir. Crit. Care Med. 187, 476-485 (2013).
71. Huang, Y. J., et al. Mouse taste buds use serotonin as a neurotransmitter. J. Neurosci. 25, 843-847 (2005).
72. Erspamer, V. Pharmacology of indolealkylamines. Pharmacol. Rev. 6, 425-487 (1954).
73. Berger, M., Gray, J. A., & Roth, B. L. The expanded biology of serotonin. Annu. Rev. Med. 60, 355-366 (2009).
74. Langer, C., et al. Atrial fibrillation in carcinoid heart disease: the role of serotonin. A review of the literature. Clin. Res. Cardiol. 96, 114-118 (2007).
75. de Jong, J. S., & Dekker, L. R. Platelets and cardiac arrhythmia. Front. Physiol. 1, 166 (2010).
76. Brattelid, T., et al. Functional serotonin 5 HT4 receptors in porcine and human ventricular myocardium with increased 5 HT4 mRNA in heart failure. Naunyn Schmiedebergs Arch. Pharmacol. 370, 157-166 (2004).
77. Connolly, J. M., et al. Fenfluramine disrupts the mitral valve interstitial cell response to serotonin. Am. J. Pathol. 175, 988-997 (2009).
78. Rothman, R. B., et al. Evidence for possible involvement of 5 HT2B receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation 102, 2836-2841 (2000).
79. Esteve, J. M., Launay, J. M., Kellermann, O., & Maroteaux, L. Functions of serotonin in hypoxic pulmonary vascular remodeling. Cell Biochem. Biophys. 47, 33-44 (2007).
80. Launay, J. M., et al. Function of the serotonin 5 hydroxytryptamine 2B receptor in pulmonary hypertension. Nat. Med. 8, 1129-1135 (2002).
81. Bolte, A. C., van Geijn, H. P., & Dekker, G. A. Pathophysiology of preeclampsia and the role of serotonin. Eur. J. Obstet. Gynecol. Reprod. Biol. 95, 12-21 (2001).
82. Bonnin, A., et al. A transient placental source of serotonin for the fetal forebrain. Nature 472, 347-350 (2011).
83. Jeffrey, J. J., Ehlich, L. S., & Roswit, W. T. Serotonin: an inducer of collagenase in myometrial smooth muscle cells. J. Cell. Physiol. 146, 399-406 (1991).
84. Matsuda, M., et al. Serotonin regulates mammary gland development via an autocrine-paracrine loop. Dev. Cell 6, 193-203 (2004).
85. de Jong, T. R., Veening, J. G., Waldinger, M. D., Cools, A. R., & Olivier, B. Serotonin and the neurobiology of the ejaculatory threshold. Neurosci. Biobehav. Rev. 30, 893-907 (2006).
86. Giuliano, F. 5 Hydroxytryptamine in premature ejaculation: opportunities for therapeutic intervention. Trends Neurosci. 30, 79-84 (2007).
87. Ramage, A. G. The role of central 5 hydroxytryptamine (5 HT, serotonin) receptors in the control of micturition. Br. J. Pharmacol. 147 (Suppl. 2), S120-S131 (2006).
88. Sommer, C. Serotonin in pain and analgesia: actions in the periphery. Mol. Neurobiol. 30, 117-125 (2004).
89. Braz, J. M., & Basbaum, A. I. Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits. J. Comp. Neurol. 507, 1990-2003 (2008).
90. Jann, M. W., & Slade, J. H. Antidepressant agents for the treatment of chronic pain and depression. Pharmacotherapy 27, 1571-1587 (2007).