Serotonergic modulation of murine fundic tone

Lin Xue, Michael Camilleri, G. Richard Locke, Jan A J Schuurkes, Ann Meulemans, Bernard J. Coulie, Joseph H. Szurszewski, Gianrico Farrugia

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Fundic tone is maintained through a balance of excitatory and inhibitory input to fundic smooth muscle. The aim of this study was to determine the role of serotonin (5-HT) and 5-HT receptors in modulating murine fundic tone. Muscle strips were prepared from the murine fundus. Intracellular recordings were made from circular smooth muscle cells, and the effects of 5-HT on tone and excitatory and inhibitory junction potentials evoked by electrical field stimulation (EFS) were determined. 5-HT induced a concentration-dependent contraction and smooth muscle depolarization that was tetrodotoxin resistant. The 5-HT1B/D receptor antagonists GR-127935 and BRL-155172 significantly inhibited 5-HT-induced contractions. The 5-HT1B/D agonist sumatriptan contracted murine fundic muscle. The 5-HT1A receptor agonist buspirone relaxed fundic smooth muscle, and the relaxation was inhibited by WAY-100135 but not by Nω-nitro-L-arginine or tetrodotoxin. 5-HT enhanced both the excitatory and inhibitory responses to EFS. The 5-HT3 receptor antagonist MDL-72222 partly inhibited both the excitatory and inhibitory response elicited by EFS, whereas the 5-HT4 receptor antagonist GR-113808 partly inhibited the EFS-evoked inhibitory response. The 5-HT reuptake inhibitor fluoxetine contracted smooth muscle strips, a contraction that was partially inhibited by GR-127935 and abolished by tetrodotoxin. In conclusion, the data suggest that 5-HT modulates murine fundic contractile activity through several different receptor subtypes. Sustained release of 5-HT maintains fundic tone through postjunctional 5-HT1B/D receptors. 5-HT3 receptors modulate excitatory neural input to murine fundic smooth muscle, and both 5-HT3 and 5-HT4 receptors modulate inhibitory neural input to murine fundic smooth muscle.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume291
Issue number6
DOIs
StatePublished - Dec 2006

Fingerprint

Serotonin
Smooth Muscle
Electric Stimulation
Tetrodotoxin
Receptors, Serotonin, 5-HT4
Receptor, Serotonin, 5-HT1B
Serotonin 5-HT1 Receptor Agonists
Receptors, Serotonin, 5-HT3
Serotonin 5-HT4 Receptor Antagonists
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT3 Receptor Antagonists
Buspirone
Sumatriptan
Muscles
Receptor, Serotonin, 5-HT1A
Muscle Relaxation
Fluoxetine
Serotonin Receptors
Evoked Potentials
Smooth Muscle Myocytes

Keywords

  • Enteric nerves
  • Fundic accommodation
  • Receptors
  • Serotonin
  • Smooth muscle

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Serotonergic modulation of murine fundic tone. / Xue, Lin; Camilleri, Michael; Locke, G. Richard; Schuurkes, Jan A J; Meulemans, Ann; Coulie, Bernard J.; Szurszewski, Joseph H.; Farrugia, Gianrico.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 291, No. 6, 12.2006.

Research output: Contribution to journalArticle

Xue, Lin ; Camilleri, Michael ; Locke, G. Richard ; Schuurkes, Jan A J ; Meulemans, Ann ; Coulie, Bernard J. ; Szurszewski, Joseph H. ; Farrugia, Gianrico. / Serotonergic modulation of murine fundic tone. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2006 ; Vol. 291, No. 6.
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AU - Xue, Lin

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AU - Locke, G. Richard

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AU - Szurszewski, Joseph H.

AU - Farrugia, Gianrico

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N2 - Fundic tone is maintained through a balance of excitatory and inhibitory input to fundic smooth muscle. The aim of this study was to determine the role of serotonin (5-HT) and 5-HT receptors in modulating murine fundic tone. Muscle strips were prepared from the murine fundus. Intracellular recordings were made from circular smooth muscle cells, and the effects of 5-HT on tone and excitatory and inhibitory junction potentials evoked by electrical field stimulation (EFS) were determined. 5-HT induced a concentration-dependent contraction and smooth muscle depolarization that was tetrodotoxin resistant. The 5-HT1B/D receptor antagonists GR-127935 and BRL-155172 significantly inhibited 5-HT-induced contractions. The 5-HT1B/D agonist sumatriptan contracted murine fundic muscle. The 5-HT1A receptor agonist buspirone relaxed fundic smooth muscle, and the relaxation was inhibited by WAY-100135 but not by Nω-nitro-L-arginine or tetrodotoxin. 5-HT enhanced both the excitatory and inhibitory responses to EFS. The 5-HT3 receptor antagonist MDL-72222 partly inhibited both the excitatory and inhibitory response elicited by EFS, whereas the 5-HT4 receptor antagonist GR-113808 partly inhibited the EFS-evoked inhibitory response. The 5-HT reuptake inhibitor fluoxetine contracted smooth muscle strips, a contraction that was partially inhibited by GR-127935 and abolished by tetrodotoxin. In conclusion, the data suggest that 5-HT modulates murine fundic contractile activity through several different receptor subtypes. Sustained release of 5-HT maintains fundic tone through postjunctional 5-HT1B/D receptors. 5-HT3 receptors modulate excitatory neural input to murine fundic smooth muscle, and both 5-HT3 and 5-HT4 receptors modulate inhibitory neural input to murine fundic smooth muscle.

AB - Fundic tone is maintained through a balance of excitatory and inhibitory input to fundic smooth muscle. The aim of this study was to determine the role of serotonin (5-HT) and 5-HT receptors in modulating murine fundic tone. Muscle strips were prepared from the murine fundus. Intracellular recordings were made from circular smooth muscle cells, and the effects of 5-HT on tone and excitatory and inhibitory junction potentials evoked by electrical field stimulation (EFS) were determined. 5-HT induced a concentration-dependent contraction and smooth muscle depolarization that was tetrodotoxin resistant. The 5-HT1B/D receptor antagonists GR-127935 and BRL-155172 significantly inhibited 5-HT-induced contractions. The 5-HT1B/D agonist sumatriptan contracted murine fundic muscle. The 5-HT1A receptor agonist buspirone relaxed fundic smooth muscle, and the relaxation was inhibited by WAY-100135 but not by Nω-nitro-L-arginine or tetrodotoxin. 5-HT enhanced both the excitatory and inhibitory responses to EFS. The 5-HT3 receptor antagonist MDL-72222 partly inhibited both the excitatory and inhibitory response elicited by EFS, whereas the 5-HT4 receptor antagonist GR-113808 partly inhibited the EFS-evoked inhibitory response. The 5-HT reuptake inhibitor fluoxetine contracted smooth muscle strips, a contraction that was partially inhibited by GR-127935 and abolished by tetrodotoxin. In conclusion, the data suggest that 5-HT modulates murine fundic contractile activity through several different receptor subtypes. Sustained release of 5-HT maintains fundic tone through postjunctional 5-HT1B/D receptors. 5-HT3 receptors modulate excitatory neural input to murine fundic smooth muscle, and both 5-HT3 and 5-HT4 receptors modulate inhibitory neural input to murine fundic smooth muscle.

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KW - Fundic accommodation

KW - Receptors

KW - Serotonin

KW - Smooth muscle

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