Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors

Mira M. Wouters, Simon J. Gibbons, Jaime L. Roeder, Marne Distad, Yijun Ou, Peter R. Strege, Joseph H. Szurszewski, Gianrico Farrugia

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Background & Aims: Interstitial cells of Cajal (ICC) are required for normal gastrointestinal motility. Loss of ICC is associated with several motility disorders. The mechanisms modulating ICC survival and proliferation are poorly understood. This study aimed to establish whether 5-hydroxytryptamine (5-HT) plays a role in regulating ICC proliferation. Methods: Expression of 5-HT receptor mRNA was investigated in muscle strips, in purified populations of ICC, and in identified single cells. The effect of 5-HT2B receptor ligands on ICC numbers was studied in primary cell cultures. Proliferation of ICC was determined by counting Ki67-positive cells in culture. Results: Of the 5-HT receptors known to be involved in proliferation, 5-HT2B receptor mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in jejunal muscle, whereas 5-HT1A, 5-HT1D, and 5-HT2C receptor mRNAs were not. 5-HT2B receptor mRNA was found in single ICC and cells purified by flow cytometry. Exogenous 5-HT (1 μmol/L) increased (66% ± 9%, P < .005) ICC numbers in culture. The 5-HT2 receptor antagonist, ritanserin, and the 5-HT2B receptor antagonist, SB204741, inhibited the effect of 5-HT. The 5-HT2B receptor agonist BW 723C86 induced a concentration-dependent increase in ICC number (50% ± 6% at 50 nM, P < .04) and increased ICC proliferation (25% ± 3% vs 19 ± 1% in controls, P < .03). Conclusions: These studies establish that 5-HT2B receptors are expressed on ICC. Exogenous 5-HT regulates ICC numbers through 5-HT2B receptors in part by increasing ICC proliferation. The 5-HT2B receptor may serve as a novel pathway to regulate ICC numbers.

Original languageEnglish (US)
Pages (from-to)897-906
Number of pages10
JournalGastroenterology
Volume133
Issue number3
DOIs
StatePublished - Sep 2007

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Receptor, Serotonin, 5-HT2B
Interstitial Cells of Cajal
Jejunum
Serotonin
Cell Count
Cell Proliferation
Serotonin 5-HT2 Receptor Antagonists
Messenger RNA
Serotonin Receptors
Serotonin 5-HT2 Receptor Agonists
Ritanserin
Receptor, Serotonin, 5-HT2C
Muscles
Gastrointestinal Motility
Primary Cell Culture

ASJC Scopus subject areas

  • Gastroenterology

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Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors. / Wouters, Mira M.; Gibbons, Simon J.; Roeder, Jaime L.; Distad, Marne; Ou, Yijun; Strege, Peter R.; Szurszewski, Joseph H.; Farrugia, Gianrico.

In: Gastroenterology, Vol. 133, No. 3, 09.2007, p. 897-906.

Research output: Contribution to journalArticle

Wouters, Mira M. ; Gibbons, Simon J. ; Roeder, Jaime L. ; Distad, Marne ; Ou, Yijun ; Strege, Peter R. ; Szurszewski, Joseph H. ; Farrugia, Gianrico. / Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors. In: Gastroenterology. 2007 ; Vol. 133, No. 3. pp. 897-906.
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abstract = "Background & Aims: Interstitial cells of Cajal (ICC) are required for normal gastrointestinal motility. Loss of ICC is associated with several motility disorders. The mechanisms modulating ICC survival and proliferation are poorly understood. This study aimed to establish whether 5-hydroxytryptamine (5-HT) plays a role in regulating ICC proliferation. Methods: Expression of 5-HT receptor mRNA was investigated in muscle strips, in purified populations of ICC, and in identified single cells. The effect of 5-HT2B receptor ligands on ICC numbers was studied in primary cell cultures. Proliferation of ICC was determined by counting Ki67-positive cells in culture. Results: Of the 5-HT receptors known to be involved in proliferation, 5-HT2B receptor mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in jejunal muscle, whereas 5-HT1A, 5-HT1D, and 5-HT2C receptor mRNAs were not. 5-HT2B receptor mRNA was found in single ICC and cells purified by flow cytometry. Exogenous 5-HT (1 μmol/L) increased (66{\%} ± 9{\%}, P < .005) ICC numbers in culture. The 5-HT2 receptor antagonist, ritanserin, and the 5-HT2B receptor antagonist, SB204741, inhibited the effect of 5-HT. The 5-HT2B receptor agonist BW 723C86 induced a concentration-dependent increase in ICC number (50{\%} ± 6{\%} at 50 nM, P < .04) and increased ICC proliferation (25{\%} ± 3{\%} vs 19 ± 1{\%} in controls, P < .03). Conclusions: These studies establish that 5-HT2B receptors are expressed on ICC. Exogenous 5-HT regulates ICC numbers through 5-HT2B receptors in part by increasing ICC proliferation. The 5-HT2B receptor may serve as a novel pathway to regulate ICC numbers.",
author = "Wouters, {Mira M.} and Gibbons, {Simon J.} and Roeder, {Jaime L.} and Marne Distad and Yijun Ou and Strege, {Peter R.} and Szurszewski, {Joseph H.} and Gianrico Farrugia",
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T1 - Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors

AU - Wouters, Mira M.

AU - Gibbons, Simon J.

AU - Roeder, Jaime L.

AU - Distad, Marne

AU - Ou, Yijun

AU - Strege, Peter R.

AU - Szurszewski, Joseph H.

AU - Farrugia, Gianrico

PY - 2007/9

Y1 - 2007/9

N2 - Background & Aims: Interstitial cells of Cajal (ICC) are required for normal gastrointestinal motility. Loss of ICC is associated with several motility disorders. The mechanisms modulating ICC survival and proliferation are poorly understood. This study aimed to establish whether 5-hydroxytryptamine (5-HT) plays a role in regulating ICC proliferation. Methods: Expression of 5-HT receptor mRNA was investigated in muscle strips, in purified populations of ICC, and in identified single cells. The effect of 5-HT2B receptor ligands on ICC numbers was studied in primary cell cultures. Proliferation of ICC was determined by counting Ki67-positive cells in culture. Results: Of the 5-HT receptors known to be involved in proliferation, 5-HT2B receptor mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in jejunal muscle, whereas 5-HT1A, 5-HT1D, and 5-HT2C receptor mRNAs were not. 5-HT2B receptor mRNA was found in single ICC and cells purified by flow cytometry. Exogenous 5-HT (1 μmol/L) increased (66% ± 9%, P < .005) ICC numbers in culture. The 5-HT2 receptor antagonist, ritanserin, and the 5-HT2B receptor antagonist, SB204741, inhibited the effect of 5-HT. The 5-HT2B receptor agonist BW 723C86 induced a concentration-dependent increase in ICC number (50% ± 6% at 50 nM, P < .04) and increased ICC proliferation (25% ± 3% vs 19 ± 1% in controls, P < .03). Conclusions: These studies establish that 5-HT2B receptors are expressed on ICC. Exogenous 5-HT regulates ICC numbers through 5-HT2B receptors in part by increasing ICC proliferation. The 5-HT2B receptor may serve as a novel pathway to regulate ICC numbers.

AB - Background & Aims: Interstitial cells of Cajal (ICC) are required for normal gastrointestinal motility. Loss of ICC is associated with several motility disorders. The mechanisms modulating ICC survival and proliferation are poorly understood. This study aimed to establish whether 5-hydroxytryptamine (5-HT) plays a role in regulating ICC proliferation. Methods: Expression of 5-HT receptor mRNA was investigated in muscle strips, in purified populations of ICC, and in identified single cells. The effect of 5-HT2B receptor ligands on ICC numbers was studied in primary cell cultures. Proliferation of ICC was determined by counting Ki67-positive cells in culture. Results: Of the 5-HT receptors known to be involved in proliferation, 5-HT2B receptor mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in jejunal muscle, whereas 5-HT1A, 5-HT1D, and 5-HT2C receptor mRNAs were not. 5-HT2B receptor mRNA was found in single ICC and cells purified by flow cytometry. Exogenous 5-HT (1 μmol/L) increased (66% ± 9%, P < .005) ICC numbers in culture. The 5-HT2 receptor antagonist, ritanserin, and the 5-HT2B receptor antagonist, SB204741, inhibited the effect of 5-HT. The 5-HT2B receptor agonist BW 723C86 induced a concentration-dependent increase in ICC number (50% ± 6% at 50 nM, P < .04) and increased ICC proliferation (25% ± 3% vs 19 ± 1% in controls, P < .03). Conclusions: These studies establish that 5-HT2B receptors are expressed on ICC. Exogenous 5-HT regulates ICC numbers through 5-HT2B receptors in part by increasing ICC proliferation. The 5-HT2B receptor may serve as a novel pathway to regulate ICC numbers.

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