Mucosal Serotonin Signaling Is Altered in Chronic... : Official journal of the American College of Gastroenterology | ACG (original) (raw)

ORIGINAL CONTRIBUTIONS: FUNCTIONAL GI DISORDERS

Mucosal Serotonin Signaling Is Altered in Chronic Constipation but Not in Opiate-Induced Constipation

Costedio, Meagan M MD1,5; Coates, Matthew D MD2,5; Brooks, Elice M BS2; Glass, Lisa M MD2; Ganguly, Eric K MD3; Blaszyk, Hagen MD4; Ciolino, Allison L MD4; Wood, Michael J MD1; Strader, Doris MD3; Hyman, Neil H MD1; Moses, Peter L MD3; Mawe, Gary M PhD2,3

1Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont, USA

2Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont, USA

3Gastroenterology and Hepatology Division of the Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA

4Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA

5M.M.C. and M.D.C. contributed equally to this work, with M.M.C. concentrating primarily on the chronic constipation arm of the study and M.D.C. working primarily on the opiate constipation experiments

Correspondence: Gary M. Mawe, PhD, Department of Anatomy and Neurobiology, University of Vermont College of Medicine, D403A Given Building, Burlington, Vermont 05405, USA. E-mail: [email protected]

published online 15 December 2009

Received 5 August 2009; accepted 2 November 2009

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.