Mucosal serotonin signaling is altered in chronic constipation but not in opiate-induced constipation.
OBJECTIVE
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.
Costedio
Meagan M
MM
Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Coates
Matthew D
MD
Brooks
Elice M
EM
Glass
Lisa M
LM
Ganguly
Eric K
EK
Blaszyk
Hagen
H
Ciolino
Allison L
AL
Wood
Michael J
MJ
Strader
Doris
D
Hyman
Neil H
NH
Moses
Peter L
PL
Mawe
Gary M
GM
D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D000704:Analysis of Variance; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002908:Chronic Disease; D003248:Constipation / Q000209:etiology* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D055815:Young Adult
D000701:Analgesics, Opioid; D005819:Genetic Markers; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin