Pauwelyn V, Lefebvre R A
Department of Pharmacology - Heymans Institute, Ghent University, Ghent, Belgium.
Neurogastroenterol Motil. 2017 Aug;29(8). doi: 10.1111/nmo.13064. Epub 2017 Mar 23.
In the gastrointestinal tract of several species, facilitating 5-HT receptors were proposed on myenteric cholinergic neurons innervating smooth muscle by in vitro study of the effect of the selective 5-HT receptor agonist prucalopride on submaximal cholinergic contractions. This was not yet established in the murine gastrointestinal tract.
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.
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 0.03 μmol/L onwards. The facilitation in the different series with 0.03 μmol/L prucalopride ranged from 41% to 104%, 30% to 76% and 24% to 74% in fundus, jejunum, and colon, respectively. The effect of 0.03 μmol/L prucalopride was concentration-dependently inhibited by GR 113808.
CONCLUSIONS & INFERENCES: In the murine gastrointestinal tract, activation of 5-HT 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.
在几种物种的胃肠道中，通过对选择性5-羟色胺（5-HT）受体激动剂普芦卡必利对次最大胆碱能收缩作用的体外研究，提出在支配平滑肌的肠肌层胆碱能神经元上存在易化性5-HT受体。这在小鼠胃肠道中尚未得到证实。
在来自小鼠胃底、空肠和结肠的环形平滑肌条中，在胍乙啶、L-精氨酸甲酯（L-NAME）存在的情况下，通过电场刺激诱导收缩，对于结肠还使用了MRS 2500。诱导次最大收缩以研究普芦卡必利的影响。
在降低电压下的电场刺激诱导了可重复的次最大神经源性和胆碱能收缩，因为这些收缩被河豚毒素和阿托品消除。六甲铵没有系统性抑制作用，但美加明降低了反应，表明部分胆碱能反应是由于节前神经元的激活。普芦卡必利浓度依赖性地增加了三种组织类型中的次最大胆碱能收缩，从0.03μmol/L起达到最大值。在胃底、空肠和结肠中，0.03μmol/L普芦卡必利在不同系列中的易化作用分别为41%至104%、30%至76%和24%至74%。0.03μmol/L普芦卡必利的作用被GR 113808浓度依赖性抑制。
在小鼠胃肠道中，普芦卡必利激活5-HT受体可增强胆碱能收缩，说明肠肌层胆碱能神经传递得到易化。普芦卡必利的增强程度与先前在其他物种中报道的相似，但有效浓度低于其他物种胃肠道所需的浓度。
