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Am J Physiol Gastrointest Liver Physiol 291: G1180-G1186, 2006. First published July 27, 2006; doi:10.1152/ajpgi.00224.2006
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NEUROREGULATION AND MOTILITY

Serotonergic modulation of murine fundic tone

Lin Xue,1 Michael Camilleri,1 G. Richard Locke, III,1 Jan A. J. Schuurkes,2 Ann Meulemans,2 Bernard J. Coulie,2 Joseph H. Szurszewski,1 and Gianrico Farrugia1

1Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester, Minnesota; and 2Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium

Submitted 19 May 2006 ; accepted in final form 26 July 2006

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 N{omega}-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.

receptors; smooth muscle; enteric nerves; fundic accommodation; serotonin


Address for reprint requests and other correspondence: G. Farrugia, Enteric NeuroScience Program, Div. of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905 (e-mail: farrugia.gianrico{at}mayo.edu)






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