Review article: the many potential roles of intestinal serotonin (5‐hydroxytryptamine, 5‐HT) signalling in inflammatory bowel disease

M. D. Coates; I. Tekin; K. E. Vrana; G. M. Mawe

doi:10.1111/apt.14226

journal article Jul 24, 2017

Review article: the many potential roles of intestinal serotonin (5‐hydroxytryptamine, 5‐HT) signalling in inflammatory bowel disease

M. D. Coates

I. Tekin K. E. Vrana G. M. Mawe

Alimentary Pharmacology & Therapeutics Vol. 46 No. 6 pp. 569-580 · Wiley

View at Publisher Save 10.1111/apt.14226

Abstract

SummaryBackgroundSerotonin (5‐hydroxytryptamine, 5‐HT) is an important mediator of every major gut‐related function. Recent investigations also suggest that 5‐HT can influence the development and severity of inflammation within the gut, particularly in the setting of inflammatory bowel disease (IBD).AimTo review the roles that the intestinal serotonin signalling system plays in gut function, with a specific focus on IBD.MethodsWe reviewed manuscripts from 1952 to 2017 that investigated and discussed roles for 5‐HT signalling in gastrointestinal function and IBD, as well as the influence of inflammation on 5‐HT signalling elements within the gut.ResultsInflammation appears to affect every major element of intestinal 5‐HT signalling, including 5‐HT synthesis, release, receptor expression and reuptake capacity. Importantly, many studies (most utilising animal models) also demonstrate that modulation of selective serotonergic receptors (via agonism of 5‐HT4R and antagonism of 5‐HT3R) or 5‐HT signal termination (via serotonin reuptake inhibitors) can alter the likelihood and severity of intestinal inflammation and/or its complicating symptoms. However, there are few human studies that have studied these relationships in a targeted manner.ConclusionsInsights discussed in this review have strong potential to lead to new diagnostic and therapeutic tools to improve the management of IBD and other related disorders. Specifically, strategies that focus on modifying the activity of selective serotonin receptors and reuptake transporters in the gut could be effective for controlling disease activity and/or its associated symptoms. Further studies in humans are required, however, to more completely understand the pathophysiological mechanisms underlying the roles of 5‐HT in this setting.

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References

107

[1]

10.1038/169800b0

[2]

10.1007/s10620-015-3598-8

[3]

10.1016/j.tins.2016.06.007

[4]

10.1046/j.1365-2036.1999.00002.x-i2

[5]

10.1111/j.1749-6632.1998.tb11120.x

[6]

10.1021/bi015722x

[7]

10.1113/jphysiol.1958.sp005940

[8]

10.1111/j.1476-5381.1958.tb00236.x

[9]

10.1113/jphysiol.1959.sp006175

[10]

10.1053/gast.2001.29567

[11]

10.1152/ajpregu.00442.2002

[12]

10.1152/ajpgi.2001.280.6.g1099

[13]

10.1172/jci12467

[14]

10.1152/ajpgi.2002.282.1.g16

[15]

10.1159/000201355

[16]

10.1124/jpet.103.053256

[17]

10.3389/fncel.2015.00487

[18]

10.1113/jp270183

[19]

10.1113/jp270182

[20]

10.1097/med.0b013e32835bc703

[21]

10.1111/j.1365-2036.2004.02180.x

[22]

10.1016/0163-7258(94)90009-4

[23]

10.1152/ajpgi.00292.2001

[24]

10.1016/s0306-4522(00)00363-8

[25]

10.1111/j.1469-7793.1998.717bm.x

[26]

10.1254/jjp.74.209

[27]

10.1021/cn300186b

[28]

10.1038/ctg.2012.8

[29]

10.1152/ajpgi.1998.275.3.g433

[30]

10.1523/jneurosci.21-16-06348.2001

[31]

10.1523/jneurosci.16-07-02352.1996

[32]

10.1016/s0074-7742(08)60526-7

[33]

10.1053/j.gastro.2004.03.013

[34]

10.2165/00002018-199920030-00007

[35]

10.1111/j.1365-2036.1994.tb00273.x

[36]

10.1136/gut.35.4.496

[37]

10.1111/j.1365-2982.2008.01247.x

[38]

10.1053/j.gastro.2011.10.001

[39]

10.15585/mmwr.mm6542a3

[40]

10.1007/s10620-012-2504-x

[41]

10.2147/ceg.s58152

[42]

10.1097/mib.0b013e31829614c6

[43]

10.1136/gutjnl-2012-304066

[44]

10.1097/mib.0000000000000763

[45]

10.1007/s004180050445

[46]

10.1152/ajpgi.00488.2002

[47]

10.1113/jphysiol.2004.062174

[48]

10.1111/j.1365-2982.2005.00719.x

[49]

10.1136/gut.2006.102780

[50]

10.3892/mmr.2016.5902

Showing 50 of 107 references

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Metrics

95

Citations

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References

Details

Published: Jul 24, 2017
Vol/Issue: 46(6)
Pages: 569-580
License: View

Authors

M

M. D. Coates

Department of Medicine Division of Gastroenterology & Hepatology Penn State Hershey Medical Center Hershey PA USA

I

I. Tekin

Neuroscience Institute University of California at Santa Barbara Santa Barbara CA USA

K

K. E. Vrana

Department of Pharmacology Penn State College of Medicine Hershey PA USA

G

G. M. Mawe

Department of Neurological Sciences University of Vermont College of Medicine Burlington VT USA

Funding

National Institutes of Health Award: DK 62267

MDC

Cite This Article

M. D. Coates, I. Tekin, K. E. Vrana, et al. (2017). Review article: the many potential roles of intestinal serotonin (5‐hydroxytryptamine, 5‐HT) signalling in inflammatory bowel disease. Alimentary Pharmacology & Therapeutics, 46(6), 569-580. https://doi.org/10.1111/apt.14226

Review article: the many potential roles of intestinal serotonin (5‐hydroxytryptamine, 5‐HT) signalling in inflammatory bowel disease

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