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 language | English (US) |
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Pages (from-to) | G1180-G1186 |
Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
Volume | 291 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2006 |
Keywords
- Enteric nerves
- Fundic accommodation
- Receptors
- Serotonin
- Smooth muscle
ASJC Scopus subject areas
- Physiology
- Hepatology
- Gastroenterology
- Physiology (medical)