Mechanisms Mediating Serotonin‐induced Contraction of Colonic Myocytes

Xu, Long; Yu, Baoping; Chen, Jianguo; Luo, Hesheng

doi:10.1111/j.1440-1681.2007.04465.x

Cited by 13 publications

(11 citation statements)

References 36 publications

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“…We observed that stimulation with 5-HT, SP, histamine and PGE 2 resulted in a concentrationdependent decrease in SMC length in the present study. These result of 5-HT and PGE 2 obtained by the cell imaging method is consistent with previous data obtained using the conventional method (17,18). Although the effects of SP, histamine and KCl on SMCs have not been fully described, here we confirmed contraction of SMC by histamine, SP and high KCl in isolated murine SMC.…”

Section: Discussionsupporting

confidence: 95%

Contraction of gut smooth muscle cells assessed by fluorescence imaging

Tokita

Akiho

Nakamura

et al. 2015

Journal of Pharmacological Sciences

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Here we discuss the development of a novel cell imaging system for the evaluation of smooth muscle cell (SMC) contraction. SMCs were isolated from the circular and longitudinal muscular layers of mouse small intestine by enzymatic digestion. SMCs were stimulated by test agents, thereafter fixed in acrolein. Actin in fixed SMCs was stained with phalloidin and cell length was determined by measuring diameter at the large end of phalloidin-stained strings within the cells. The contractile response was taken as the decrease in the average length of a population of stimulated-SMCs. Various mediators and chemically identified compounds of daikenchuto (DKT), pharmaceutical-grade traditional Japanese prokinetics, were examined. Verification of the integrity of SMC morphology by phalloidin and DAPI staining and semi-automatic measurement of cell length using an imaging analyzer was a reliable method by which to quantify the contractile response. Serotonin, substance P, prostaglandin E2 and histamine induced SMC contraction in concentration-dependent manner. Two components of DKT, hydroxy-α-sanshool and hydroxy-β-sanshool, induced contraction of SMCs. We established a novel cell imaging technique to evaluate SMC contractility. This method may facilitate investigation into SMC activity and its role in gastrointestinal motility, and may assist in the discovery of new prokinetic agents.

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Section: Discussionsupporting

confidence: 95%

Contraction of gut smooth muscle cells assessed by fluorescence imaging

Tokita

Akiho

Nakamura

et al. 2015

Journal of Pharmacological Sciences

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“…One prior study showed that FMT had the high efficiency to improve the syndrome of STC [33], which suggested that normal gut microbiota could benefit to gastrointestinal motor function. In addition, Xu et al [11] also found 5-HT could lead to the contraction of isolated smooth muscle cell, and cell length would be shortened in a 5-HT dose-dependent manner. In our study, after antibiotics treatments, the abundance of gut microbiota decreased significantly in mice, which were also named pseudo-germ-free mice.…”

Section: Discussionmentioning

confidence: 99%

“…Fukumoto et al [10] reported that 5-HT from ECs could stimulate 5-HT 3 receptors which were located on the vagal sensory fibers, and the sensory information was transferred to the vagal efferent or it stimulated the release of acetylcholine which affected muscle contraction. 5-HT could also cause the release of Ca 2+ from the sarcoplasmic reticulum after it activated 5-HT 3 receptors and the inositol 1,4,5-trisphosphate pathway, which induced contraction of colonic myocytes [11]. Yano et al [12] suggested that gut microbes regulated the 5-HT level in colon, which impacted intestinal motility and hemostasis.…”

Section: Introductionmentioning

confidence: 99%

Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility

et al. 2017

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BackgroundThe gastrointestinal motility is affected by gut microbiota and the relationship between them has become a hot topic. However, mechanisms of microbiota in regulating motility have not been well defined. We thus investigated the effect of microbiota depletion by antibiotics on gastrointestinal motility, colonic serotonin levels, and bile acids metabolism.MethodsAfter 4 weeks with antibiotics treatments, gastrointestinal and colon transit, defecation frequency, water content, and other fecal parameters were measured and analyzed in both wild-type and antibiotics-treated mice, respectively. Contractility of smooth muscle, serotonin levels, and bile acids levels in wild-type and antibiotics-treated mice were also analyzed.ResultsAfter antibiotics treatment, the richness and diversity of intestinal microbiota decreased significantly, and the fecal of mice had less output (P < 0.01), more water content (P < 0.01), and longer pellet length (P < 0.01). Antibiotics treatment in mice also resulted in delayed gastrointestinal and colonic motility (P < 0.05), and inhibition of phasic contractions of longitudinal muscle from isolated proximal colon (P < 0.01). In antibiotics-treated mice, serotonin, tryptophan hydroxylase 1, and secondary bile acids levels were decreased.ConclusionGut microbiota play an important role in the regulation of intestinal bile acids and serotonin metabolism, which could probably contribute to the association between gut microbiota and gastrointestinal motility as intermediates.

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“…Interestingly, secondary BAs were proposed to directly act on ECs to synthetize 5-HT by elevating colonic TPH1 expression 23 . 5-HT was reported to induce the contraction of colonic myocytes due to the release of Ca 2+ from the sarcoplasmic reticulum by activating 5-HT 3 receptors and the inositol 1, 4, 5-trisphosphate pathway 24 .…”

Section: Introductionmentioning

confidence: 99%

Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility

Zhao

Ding

et al. 2017

Sci Rep

172

122

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The gut microbiota is involved in various physiological functions, and disturbances in the host-microbiome have been proven to contribute to the dysfunction of gut; however, whether microbiota participates in the pathogenesis of constipation remains unclear. In this study, we extracted and analyzed microbiota in feces from constipated donors who had undergone effective therapy with fecal microbiota transplantation, transplanted microbiota into pseudo-germ-free mice, and measured gut motility. These mice presented with lower pellet frequency and water percentage, smaller pellet size, delayed gastrointestinal transit time, and weaker spontaneous contractions of colonic smooth muscle. To determine the mechanism underlying delayed gut motility, microbial metabolites were measured. Short chain fatty acids and secondary bile acids were decreased in mice receiving microbiota from constipated donors. Moreover, the compositional changes of gut microbiota in constipated patients were identified, including the operational taxonomic unit, and the species richness and α diversity were much greater than those in healthy volunteers. These findings suggest that alterations of the microbiome might affect gut motility via altered microbial-derived metabolites in the development of constipation, and the restoration of disturbed microbiota might improve the clinical phenotype. This study indicates that regulating the intestinal environment may be a novel therapy strategy for constipation.

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Mechanisms Mediating Serotonin‐induced Contraction of Colonic Myocytes

Cited by 13 publications

References 36 publications

Contraction of gut smooth muscle cells assessed by fluorescence imaging

Contraction of gut smooth muscle cells assessed by fluorescence imaging

Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility

Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility

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