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 Scopus citations

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)
Pages (from-to)G1180-G1186
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume291
Issue number6
DOIs
StatePublished - Dec 1 2006

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Serotonergic modulation of murine fundic tone'. Together they form a unique fingerprint.

  • Cite this

    Xue, L., Camilleri, M., Locke, G. R., Schuurkes, J. A. J., Meulemans, A., Coulie, B. J., Szurszewski, J. H., & Farrugia, G. (2006). Serotonergic modulation of murine fundic tone. American Journal of Physiology - Gastrointestinal and Liver Physiology, 291(6), G1180-G1186. https://doi.org/10.1152/ajpgi.00224.2006