Alterations in melatonin and 5‐HT signalling in the colonic mucosa of mice with dextran‐sodium sulfate‐induced colitis

Sarah J. MacEachern, Catherine M. Keenan, Evangelia Papakonstantinou, Keith A. Sharkey, Bhavik Patel

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal 5‐HT (serotonin) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co‐released with 5‐HT from the mucosa and has a wide variety of actions in the GI tract. Here, we examined how melatonin signalling is affected by colitis and determined how this relates to 5‐HT signalling. Experimental Approach Using electroanalytical approaches, we investigated how 5‐HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)‐induced colitis in mice. Studies were conducted to explore if melatonin treatment during active colitis could reduce the severity of colitis. Key Results We observed an increase in 5‐HT and a decrease in melatonin availability in DSS‐induced colitis. A significant reduction in 5‐HT reuptake was observed in DSS‐induced colitis animals. A reduction in the content of 5‐HT was observed, but no difference in tryptophan levels were observed. A reduction in deoxycholic acid‐stimulated 5‐HT availability and a significant reduction in mechanically‐stimulated 5‐HT and melatonin availability were observed in DSS‐induced colitis. Orally or rectally administered melatonin once colitis was established did not significantly suppress inflammation. Conclusion and Implications Our data suggest that DSS‐induced colitis results in a reduction in melatonin availability and an increase in 5‐HT availability, due to a reduction/loss of tryptophan hydroxylase 1 enzyme, 5‐HT content and 5‐HT transporters. Mechanosensory release was more susceptible to inflammation when compared with chemosensory release.
Original languageEnglish
Pages (from-to)1535-1547
JournalBritish Journal of Pharmacology
Volume175
Issue number9
DOIs
Publication statusPublished - 25 Mar 2018

Bibliographical note

This is the peer reviewed version of the following article: MacEachern, S. J., Keenan, C. M., Papakonstantinou, E., Sharkey, K. A., and Patel, B. A. (2018) Alterations in melatonin and 5‐HT signalling in the colonic mucosa of mice with dextran‐sodium sulfate‐induced colitis. British Journal of Pharmacology, which has been published in final form at https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14163. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Fingerprint

Dive into the research topics of 'Alterations in melatonin and 5‐HT signalling in the colonic mucosa of mice with dextran‐sodium sulfate‐induced colitis'. Together they form a unique fingerprint.

Cite this