Serotonergic modulation of murine fundic tone.
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-HT(1B/D) receptor antagonists GR-127935 and BRL-155172 significantly inhibited 5-HT-induced contractions. The 5-HT(1B/D) agonist sumatriptan contracted murine fundic muscle. The 5-HT(1A) receptor agonist buspirone relaxed fundic smooth muscle, and the relaxation was inhibited by WAY-100135 but not by N(omega)-nitro-l-arginine or tetrodotoxin. 5-HT enhanced both the excitatory and inhibitory responses to EFS. The 5-HT(3) receptor antagonist MDL-72222 partly inhibited both the excitatory and inhibitory response elicited by EFS, whereas the 5-HT(4) 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-HT(1B/D) receptors. 5-HT(3) receptors modulate excitatory neural input to murine fundic smooth muscle, and both 5-HT(3) and 5-HT(4) receptors modulate inhibitory neural input to murine fundic smooth muscle.
Xue
Lin
L
Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Camilleri
Michael
M
Locke
G Richard
GR
Schuurkes
Jan A J
JA
Meulemans
Ann
A
Coulie
Bernard J
BJ
Szurszewski
Joseph H
JH
Farrugia
Gianrico
G
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology*; D005748:Gastric Fundus / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D008297:Male; D051379:Mice; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage*
D012701:Serotonin