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


eMediNexus    11 November 2017

The goal of a recent study published in Neurogastroenterology and Motility was to establish that facilitating 5 HT4 receptors on myenteric cholinergic neurons innervating smooth muscle in the murine gastrointestinal tract by in vitro study of the effect of the selective 5 HT4 receptor agonist prucalopride on submaximal cholinergic contractions. In this experiment contractions were induced in circular smooth muscle strips from murine fundus jejunum and colon by electrical field stimulation in the presence of guanethidine L NAME along with MRS 2500 for colon. Herein submaximal contractions were induced to study the influence of prucalopride. The results showed that 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 indicating that part of the cholinergic response is due to the activation of preganglionic neurons. Additionally prucalopride concentration dependently increased the submaximal cholinergic contractions in the three tissue types reaching maximum from 0.03 956 mol L onwards. The facilitation in the different series with 0.03 956 mol L prucalopride ranged from 41 to 104 30 to 76 and 24 to 74 in fundus jejunum and colon respectively. Whereas the effect of 0.03 956 mol L prucalopride was concentration dependently inhibited by GR 113808. Thus it was concluded that in murine gastrointestinal tract activation of 5 HT4 receptors with prucalopride enhances cholinergic contractions illustrating facilitation of myenteric cholinergic neurotransmission. It was stated that 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.1 Reference 1. Pauwelyn V Lefebvre R. 5 HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract. Neurogastroenterology Motility. 2017 29 8 e13064. doi 10.1111 nmo.13064.

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