Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation

Meagan M. Costedio, Matthew Coates, Elice M. Brooks, Lisa M. Glass, Eric K. Ganguly, Hagen Blaszyk, Allison L. Ciolino, Michael J. Wood, Doris Strader, Neil H. Hyman, Peter L. Moses, Gary M. Mawe

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES: Changes in mucosal serotonin (5-HT) signaling have been detected in a number of functional and inflammatory disorders of the gastrointestinal (GI) tract. This study was undertaken to determine whether chronic constipation (CC) is associated with disordered 5-HT signaling and to evaluate whether constipation caused by opiate use causes such changes.METHODS: Human rectal biopsy samples were obtained from healthy volunteers, individuals with idiopathic CC, and individuals taking opiate medication with or without occurrence of constipation. EC cells were identified by 5-HT immunohistochemistry. 5-HT content and release levels were determined by enzyme immunoassay, and mRNA levels for the synthetic enzyme tryptophan hydroxylase-1 (TpH-1) and serotonin-selective reuptake transporter (SERT) were assessed by quantitative real-time reverse transcription PCR.RESULTS: CC was associated with increases in TpH-1 transcript, 5-HT content, and 5-HT release under basal and stimulated conditions, whereas EC cell numbers and SERT transcript levels were not altered. No changes in these elements of 5-HT signaling were detected in opiate-induced constipation (OIC).CONCLUSIONS: These findings demonstrate that CC is associated with a pattern of altered 5-HT signaling that leads to increased 5-HT availability but does not involve a decrease in SERT expression. It is possible that increased 5-HT availability due to increased synthesis and release contributes to constipation due to receptor desensitization. Furthermore, the finding that elements of 5-HT signaling were not altered in the mucosa of individuals with OIC indicates that constipation as a condition does not lead to compensatory changes in 5-HT synthesis, release, or signal termination.

Original languageEnglish (US)
Pages (from-to)1173-1180
Number of pages8
JournalAmerican Journal of Gastroenterology
Volume105
Issue number5
DOIs
StatePublished - May 1 2010

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Opiate Alkaloids
Constipation
Serotonin
Tryptophan Hydroxylase

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Costedio, Meagan M. ; Coates, Matthew ; Brooks, Elice M. ; Glass, Lisa M. ; Ganguly, Eric K. ; Blaszyk, Hagen ; Ciolino, Allison L. ; Wood, Michael J. ; Strader, Doris ; Hyman, Neil H. ; Moses, Peter L. ; Mawe, Gary M. / Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation. In: American Journal of Gastroenterology. 2010 ; Vol. 105, No. 5. pp. 1173-1180.
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title = "Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation",
abstract = "OBJECTIVES: Changes in mucosal serotonin (5-HT) signaling have been detected in a number of functional and inflammatory disorders of the gastrointestinal (GI) tract. This study was undertaken to determine whether chronic constipation (CC) is associated with disordered 5-HT signaling and to evaluate whether constipation caused by opiate use causes such changes.METHODS: Human rectal biopsy samples were obtained from healthy volunteers, individuals with idiopathic CC, and individuals taking opiate medication with or without occurrence of constipation. EC cells were identified by 5-HT immunohistochemistry. 5-HT content and release levels were determined by enzyme immunoassay, and mRNA levels for the synthetic enzyme tryptophan hydroxylase-1 (TpH-1) and serotonin-selective reuptake transporter (SERT) were assessed by quantitative real-time reverse transcription PCR.RESULTS: CC was associated with increases in TpH-1 transcript, 5-HT content, and 5-HT release under basal and stimulated conditions, whereas EC cell numbers and SERT transcript levels were not altered. No changes in these elements of 5-HT signaling were detected in opiate-induced constipation (OIC).CONCLUSIONS: These findings demonstrate that CC is associated with a pattern of altered 5-HT signaling that leads to increased 5-HT availability but does not involve a decrease in SERT expression. It is possible that increased 5-HT availability due to increased synthesis and release contributes to constipation due to receptor desensitization. Furthermore, the finding that elements of 5-HT signaling were not altered in the mucosa of individuals with OIC indicates that constipation as a condition does not lead to compensatory changes in 5-HT synthesis, release, or signal termination.",
author = "Costedio, {Meagan M.} and Matthew Coates and Brooks, {Elice M.} and Glass, {Lisa M.} and Ganguly, {Eric K.} and Hagen Blaszyk and Ciolino, {Allison L.} and Wood, {Michael J.} and Doris Strader and Hyman, {Neil H.} and Moses, {Peter L.} and Mawe, {Gary M.}",
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Costedio, MM, Coates, M, Brooks, EM, Glass, LM, Ganguly, EK, Blaszyk, H, Ciolino, AL, Wood, MJ, Strader, D, Hyman, NH, Moses, PL & Mawe, GM 2010, 'Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation', American Journal of Gastroenterology, vol. 105, no. 5, pp. 1173-1180. https://doi.org/10.1038/ajg.2009.683

Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation. / Costedio, Meagan M.; Coates, Matthew; Brooks, Elice M.; Glass, Lisa M.; Ganguly, Eric K.; Blaszyk, Hagen; Ciolino, Allison L.; Wood, Michael J.; Strader, Doris; Hyman, Neil H.; Moses, Peter L.; Mawe, Gary M.

In: American Journal of Gastroenterology, Vol. 105, No. 5, 01.05.2010, p. 1173-1180.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation

AU - Costedio, Meagan M.

AU - Coates, Matthew

AU - Brooks, Elice M.

AU - Glass, Lisa M.

AU - Ganguly, Eric K.

AU - Blaszyk, Hagen

AU - Ciolino, Allison L.

AU - Wood, Michael J.

AU - Strader, Doris

AU - Hyman, Neil H.

AU - Moses, Peter L.

AU - Mawe, Gary M.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - OBJECTIVES: Changes in mucosal serotonin (5-HT) signaling have been detected in a number of functional and inflammatory disorders of the gastrointestinal (GI) tract. This study was undertaken to determine whether chronic constipation (CC) is associated with disordered 5-HT signaling and to evaluate whether constipation caused by opiate use causes such changes.METHODS: Human rectal biopsy samples were obtained from healthy volunteers, individuals with idiopathic CC, and individuals taking opiate medication with or without occurrence of constipation. EC cells were identified by 5-HT immunohistochemistry. 5-HT content and release levels were determined by enzyme immunoassay, and mRNA levels for the synthetic enzyme tryptophan hydroxylase-1 (TpH-1) and serotonin-selective reuptake transporter (SERT) were assessed by quantitative real-time reverse transcription PCR.RESULTS: CC was associated with increases in TpH-1 transcript, 5-HT content, and 5-HT release under basal and stimulated conditions, whereas EC cell numbers and SERT transcript levels were not altered. No changes in these elements of 5-HT signaling were detected in opiate-induced constipation (OIC).CONCLUSIONS: These findings demonstrate that CC is associated with a pattern of altered 5-HT signaling that leads to increased 5-HT availability but does not involve a decrease in SERT expression. It is possible that increased 5-HT availability due to increased synthesis and release contributes to constipation due to receptor desensitization. Furthermore, the finding that elements of 5-HT signaling were not altered in the mucosa of individuals with OIC indicates that constipation as a condition does not lead to compensatory changes in 5-HT synthesis, release, or signal termination.

AB - OBJECTIVES: Changes in mucosal serotonin (5-HT) signaling have been detected in a number of functional and inflammatory disorders of the gastrointestinal (GI) tract. This study was undertaken to determine whether chronic constipation (CC) is associated with disordered 5-HT signaling and to evaluate whether constipation caused by opiate use causes such changes.METHODS: Human rectal biopsy samples were obtained from healthy volunteers, individuals with idiopathic CC, and individuals taking opiate medication with or without occurrence of constipation. EC cells were identified by 5-HT immunohistochemistry. 5-HT content and release levels were determined by enzyme immunoassay, and mRNA levels for the synthetic enzyme tryptophan hydroxylase-1 (TpH-1) and serotonin-selective reuptake transporter (SERT) were assessed by quantitative real-time reverse transcription PCR.RESULTS: CC was associated with increases in TpH-1 transcript, 5-HT content, and 5-HT release under basal and stimulated conditions, whereas EC cell numbers and SERT transcript levels were not altered. No changes in these elements of 5-HT signaling were detected in opiate-induced constipation (OIC).CONCLUSIONS: These findings demonstrate that CC is associated with a pattern of altered 5-HT signaling that leads to increased 5-HT availability but does not involve a decrease in SERT expression. It is possible that increased 5-HT availability due to increased synthesis and release contributes to constipation due to receptor desensitization. Furthermore, the finding that elements of 5-HT signaling were not altered in the mucosa of individuals with OIC indicates that constipation as a condition does not lead to compensatory changes in 5-HT synthesis, release, or signal termination.

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JF - American Journal of Gastroenterology

SN - 0002-9270

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