Search results for "Intestinal motility"

Postnatal development of the dopaminergic signaling involved in the modulation of intestinal motility in mice

2015

Background:Since antidopaminergic drugs are pharmacological agents employed in the management of gastrointestinal motor disorders at all ages, we investigated whether the enteric dopaminergic system may undergo developmental changes after birth.Methods:Intestinal mechanical activity was examined in vitro as changes in isometric tension.Results:In 2-d-old (P2) mice, dopamine induced a contractile effect, decreasing in intensity with age, replaced, at the weaning (day 20), by a relaxant response. Both responses were tetrodotoxin (TTX)-insensitive. In P2, dopaminergic contraction was inhibited by D1-like receptor antagonist and mimicked by D1-like receptor agonist. In 90-d-old (P90) mice, the …

Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.

2018

Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt(−)). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon. HGprt(−) tissues showed a lower in amplitude spontaneous activity and atropine-sensitivity neural contraction compared to control mice. The responses to carbachol a…

Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility

2018

International audience; Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut dev…

Angiotensin II type II receptors and colonic dysmotility in 2,4-dinitrofluorobenzenesulfonic acid-induced colitis in rats

2016

Background: Angiotensin II (Ang II), the main peptide of the renin-angiotensin system (RAS), has been suggested to be involved in inflammatory bowel diseases. Since RAS has emerged as gut motility regulator, and dysmotility is associated with intestinal inflammation, our objective was to investigate in rat 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis the functionality of RAS and its contribution to colonic motor alterations. Methods: The effects of Ang II on the longitudinal colonic muscular contractility of control and DNBS-treated rats were characterized in vitro. Transcripts encoding for Ang II receptors were investigated by RT-PCR. Key Results: Inflamed preparations showed a l…

Opposite effects of dopamine on the mechanical activity of circular and longitudinal muscle of human colon.

2020

Background Because dopamine (DA) has gained increasing evidence as modulator of gut motility, we aimed to characterize dopaminergic response in human colon, evaluating function and distribution of dopamine receptors in circular vs longitudinal muscle strips. Methods Mechanical responses to DA and dopaminergic agonists on slow phasic contractions and on basal tone were examined in vitro as changes in isometric tension. RT-PCR was used to reveal the distribution of dopaminergic receptors. Key results In spontaneous active circular muscle, DA induced an increase in the amplitude of slow phasic contractions and of the basal tone, via activation of D1-like receptors. DA contractile responses wer…

Smooth muscle and neural dysfunction contribute to different phases of murine postoperative ileus.

2015

Background Postoperative ileus (POI) is characterized by a transient inhibition of gastrointestinal (GI) motility after abdominal surgery mediated by the inflammation of the muscularis externa (ME). The aim of this study was to identify alterations in the enteric nervous system that may contribute to the pathogenesis of POI. Methods Gastrointestinal transit, contractility of isolated smooth muscle strips and inflammatory parameters were evaluated at different time points (1.5 h to 10 days) after intestinal manipulation (IM) in mice. Immune-labeling was used to visualize changes in myenteric neurons. Key Results Intestinal manipulation resulted in an immediate inhibition of GI transit recove…

NEW THERAPEUTIC PERSPECTIVES IN IRRITABLE BOWEL SYNDROME: TARGETING LOW-GRADE INFLAMMATION, IMMUNO-NEUROENDOCRINE AXIS, MOTILITY, SDECRETION AND BEYO…

2017

Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune, dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiot…

Pharmacological analysis of intrinsic neural control of rat duodenum motility in vitro

1988

Interdigestive Plasma Motilin Concentrations in Aged Adults

1986

The interdigestive plasma motilin concentrations were evaluated in 13 over-65 healthy adults with no evidence of significant disease and in 19 younger individuals. Plasma motilin levels were determined every 15 min during a 3-hr fasting period, using a radioimmunological method. The individual median values of plasma motilin concentrations during the entire study period were significantly higher in aged than younger adults. The individual median coefficients of variation of motilin concentrations and the percentage increases of plasma motilin above baseline at each peak were significantly lower in the aged than in the young group. The results of this study indicate that during the interdige…

Effect of the GLP-1 analog liraglutide on satiation and gastric sensorimotor function during nutrient-drink ingestion

2012

Background/Aim:Liraglutide, a glucagon-like peptide-1 analog, induces weight loss. We investigated whether liraglutide affects gastric accommodation and satiation by measuring the intragastric pressure (IGP) during nutrient-drink consumption and using the barostat technique.Methods:Ten healthy volunteers (HVs) were tested after placebo, 0.3, 0.6 or 1.2 mg liraglutide administration. IGP was studied during intragastric nutrient-drink (1.5 kcal ml(-1)) infusion (60 ml min(-1)), while the HVs scored their satiation on a graded scale until maximal satiation. In a separate session, isobaric distentions were performed using the barostat with stepwise increments of 2 mm Hg starting from minimal di…