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5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract

Vicky Pauwelyn (UGent) and Romain Lefebvre (UGent)
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Abstract
Background: In the gastrointestinal tract of several species, facilitating 5-HT4 receptors were proposed on myenteric cholinergic neurons innervating smooth muscle by invitro study of the effect of the selective 5-HT4 receptor agonist prucalopride on submaximal cholinergic contractions. This was not yet established in the murine gastrointestinal tract. Methods: In circular smooth muscle strips from murine fundus, jejunum and colon, contractions were induced by electrical field stimulation in the presence of guanethidine, L-NAME and for colon also MRS 2500. Submaximal contractions were induced to study the influence of prucalopride. Key Results: Electrical field stimulation at reduced voltage induced reproducible submaximal neurogenic and cholinergic contractions as the contractions were abolished by tetrodotoxin and atropine. Hexamethonium had no systematic inhibitory effect but mecamylamine reduced the responses, suggesting that part of the cholinergic response is due to activation of preganglionic neurons. Prucalopride concentration-dependently increased the submaximal cholinergic contractions in the three tissue types, reaching maximum from 0.03mol/L onwards. The facilitation in the different series with 0.03mol/L prucalopride ranged from 41% to 104%, 30% to 76% and 24% to 74% in fundus, jejunum, and colon, respectively. The effect of 0.03mol/L prucalopride was concentration-dependently inhibited by GR 113808. Conclusions & Inferences: In the murine gastrointestinal tract, activation of 5-HT4 receptors with prucalopride enhances cholinergic contractions, illustrating facilitation of myenteric cholinergic neurotransmission. The degree of enhancement with prucalopride is of similar magnitude as previously reported in other species, but the effective concentrations are lower than those needed in the gastrointestinal tract of other species.
Keywords
5-HT4 receptor, cholinergic neurotransmission, gastrointestinal tract, mouse, prucalopride, PURINERGIC NEUROMUSCULAR-TRANSMISSION, CIRCULAR SMOOTH-MUSCLE, ENTERIC NERVOUS-SYSTEM, PIG DESCENDING COLON, LONGITUDINAL MUSCLE, MYENTERIC PLEXUS, GASTRIC FUNDUS, IN-VITRO, MICE, NEURONS

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Chicago
Pauwelyn, Vicky, and Romain Lefebvre. 2017. “5-HT4 Receptors Facilitate Cholinergic Neurotransmission Throughout the Murine Gastrointestinal Tract.” Neurogastroenterology and Motility 29 (8).
APA
Pauwelyn, V., & Lefebvre, R. (2017). 5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract. NEUROGASTROENTEROLOGY AND MOTILITY , 29(8).
Vancouver
1.
Pauwelyn V, Lefebvre R. 5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract. NEUROGASTROENTEROLOGY AND MOTILITY . 2017;29(8).
MLA
Pauwelyn, Vicky, and Romain Lefebvre. “5-HT4 Receptors Facilitate Cholinergic Neurotransmission Throughout the Murine Gastrointestinal Tract.” NEUROGASTROENTEROLOGY AND MOTILITY 29.8 (2017): n. pag. Print.
@article{8532575,
  abstract     = {Background: In the gastrointestinal tract of several species, facilitating 5-HT4 receptors were proposed on myenteric cholinergic neurons innervating smooth muscle by invitro study of the effect of the selective 5-HT4 receptor agonist prucalopride on submaximal cholinergic contractions. This was not yet established in the murine gastrointestinal tract. 
Methods: In circular smooth muscle strips from murine fundus, jejunum and colon, contractions were induced by electrical field stimulation in the presence of guanethidine, L-NAME and for colon also MRS 2500. Submaximal contractions were induced to study the influence of prucalopride. 
Key Results: Electrical field stimulation at reduced voltage induced reproducible submaximal neurogenic and cholinergic contractions as the contractions were abolished by tetrodotoxin and atropine. Hexamethonium had no systematic inhibitory effect but mecamylamine reduced the responses, suggesting that part of the cholinergic response is due to activation of preganglionic neurons. Prucalopride concentration-dependently increased the submaximal cholinergic contractions in the three tissue types, reaching maximum from 0.03mol/L onwards. The facilitation in the different series with 0.03mol/L prucalopride ranged from 41\% to 104\%, 30\% to 76\% and 24\% to 74\% in fundus, jejunum, and colon, respectively. The effect of 0.03mol/L prucalopride was concentration-dependently inhibited by GR 113808. 
Conclusions \& Inferences: In the murine gastrointestinal tract, activation of 5-HT4 receptors with prucalopride enhances cholinergic contractions, illustrating facilitation of myenteric cholinergic neurotransmission. The degree of enhancement with prucalopride is of similar magnitude as previously reported in other species, but the effective concentrations are lower than those needed in the gastrointestinal tract of other species.},
  articleno    = {e13064},
  author       = {Pauwelyn, Vicky and Lefebvre, Romain},
  issn         = {1350-1925},
  journal      = {NEUROGASTROENTEROLOGY AND MOTILITY },
  keyword      = {5-HT4 receptor,cholinergic neurotransmission,gastrointestinal tract,mouse,prucalopride,PURINERGIC NEUROMUSCULAR-TRANSMISSION,CIRCULAR SMOOTH-MUSCLE,ENTERIC NERVOUS-SYSTEM,PIG DESCENDING COLON,LONGITUDINAL MUSCLE,MYENTERIC PLEXUS,GASTRIC FUNDUS,IN-VITRO,MICE,NEURONS},
  language     = {eng},
  number       = {8},
  pages        = {12},
  title        = {5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract},
  url          = {http://dx.doi.org/10.1111/nmo.13064},
  volume       = {29},
  year         = {2017},
}

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