Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT<sub>4</sub>agonist tegaserod

Grider, John R.

doi:10.1152/ajpgi.00326.2005

Cited by 29 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional support for a role of 5-HT release in propulsive motility comes from ex vivo 19, 78, 81 and in vivo 82, 83 studies demonstrating that antagonists of 5-HT 3 and/or 5-HT 4 receptors slow intestinal motility, as well as a study demonstrating that corticotropin-releasing hormone-induced defecation is reversed by peripheral actions of the 5-HT 3 receptor antagonist, ramosetron 84 . Furthermore, in isolated guinea pig colon preparations, propulsive motility is disrupted by desensitization of 5-HT 4 receptors 85 , or high concentrations of the SERT inhibitor fluoxetine 13 , which presumably leads to 5-HT receptor desensitization by increasing 5-HT concentrations in the interstitial space.…”

Section: Functions Of 5-ht In the Gastrointestinal Tractmentioning

confidence: 99%

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Mawe

Hoffman

2013

Nat Rev Gastroenterol Hepatol

899

783

View full text Add to dashboard Cite

Serotonin (5-HT) has been recognized for decades as an important signaling molecule in the gut, but it is still revealing its secrets. We continue to discover novel gastrointestinal (GI) functions of 5-HT, as well as actions of gut-derived 5-HT outside of the gut, and we are learning how 5-HT signaling is altered in GI disorders. Furthermore, new therapeutic targets related to 5-HT signaling are being identified that can hopefully be exploited to alleviate the symptoms of functional GI disorders. Conventional functions of 5-HT in the gut involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion, and vasodilation. Activation of extrinsic vagal and spinal afferent fibers results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts non-conventional actions that include serving as a pro-inflammatory signaling molecule and as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, which comes from the gut, can promote hemostasis, influence bone development, and contribute to allergic airway inflammation. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhea or constipation, respectively. More recently, the synthetic enzyme, tryptophan hydroxylase has been targeted, and there are recent findings suggesting that epithelial 5-HT4 receptors could be targeted to provide a safe and effective treatment for constipation. Here we provide an overview of these serotonergic actions and treatment strategies.

show abstract

Section: Functions Of 5-ht In the Gastrointestinal Tractmentioning

confidence: 99%

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Mawe

Hoffman

2013

Nat Rev Gastroenterol Hepatol

899

783

View full text Add to dashboard Cite

show abstract

“…5-HT released from EC cells in response to chemical or mechanical stimuli affects GI motility (12,14). 5-HT initiates peristaltic reflexes by acting on intrinsic (16,19), as well as extrinsic, sensory neurons (13).…”

Section: Discussionmentioning

confidence: 99%

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

Tsukamoto

Ariga²,

Mantyh³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

(EC) cells of the epithelial cells release 5-HT into the lumen, as well as basolateral border. However, the physiological role of released 5-HT into the lumen is poorly understood. Concentrations of 5-HT in the colonic mucosa, colonic lumen, and feces were measured by HPLC in rats. To investigate whether intraluminal 5-HT accelerates colonic transit, 5-HT and 51 Cr were administered into the lumen of the proximal colon, and colonic transit was measured. To investigate whether 5-HT is released into the lumen, we used an ex vivo model of isolated vascularly and luminally perfused rat proximal colon. To investigate whether luminal 5-HT is involved in regulating stressinduced colonic motility, the distal colonic motility was recorded under the stress loading, and a 5-HT3 receptor antagonist (ondansetron, 10 Ϫ6 M, 0.5 ml) was administered intraluminally of the distal colon. Tissue content of 5-HT in the proximal colon (15.2 Ϯ 4.3 ng/mg wet tissue) was significantly higher than that in the distal colon (3.3 Ϯ 0.7 ng/mg wet tissue), while fecal content and luminal concentration of 5-HT was almost the same between the proximal and distal colon. Luminal administration of 5-HT (10 Ϫ6 -10 Ϫ5 M) significantly accelerated colonic transit. Elevation of intraluminal pressure by 10 cmH2O significantly increased the luminal concentration of 5-HT but not the vascular concentration of 5-HT. Stress-induced stimulation of the distal colonic motility was significantly attenuated by the luminal administration of ondansetron. These results suggest that luminally released 5-HT from EC cells plays an important role in regulating colonic motility in rats. enterochromaffin cells; distal colon; luminal pressure; restraint stress SEROTONIN (5-HT) IN THE GASTROINTESTINAL (GI) tract is involved in regulating GI motility. While 5-HT acts as a neurotransmitter of the enteric nervous system (15), the majority of 5-HT is stored in enterochromaffin (EC) cells of epithelial cells.EC cells have been considered to release 5-HT mainly into the blood vessels and/or intrinsic nerve terminal via a basolateral border (14). In contrast, others showed that 5-HT is also released into the intestinal lumen in response to vagal nerve stimulation (1,20), luminal acidification (25), and food intake (10). Immunoelectron microscopic study showed the anatomical evidence that 5-HT is released from EC cells in response to an increase of luminal pressure of the rat duodenum (12). However, the physiological role of released 5-HT into the GI lumen is poorly understood.In this study, we hypothesize that luminally released 5-HT from EC cells of the proximal colon is transferred distally with feces and stimulates motility of the distal colon, resulting in acceleration of colonic transit in rats. We also investigated the mechanism of luminal release of 5-HT of the rat proximal colon.There is accumulated evidence that a variety of stress stimulates colonic motility, colonic transit, and fecal pellet output (9,21,35,38,47). Stress-induced acceleration of colonic motor function...

show abstract

“…Though it does not initiate peristaltic movement, 5-HT3 coveys any kind of change in gut motility to the brain via its presence on myenteric IPANs and in the myenteric plexus, where they mediate fast excitatory neurotransmission [75]. Similarly, 5-HT4 receptors themselves do not initiate peristaltic reflexes, but because of their location at the terminals of submucosal IPANs, at synapses within the myenteric plexus, and at the neuromuscular junction, stimulation of 5-HT4 receptors is critical for these reflexes [76]. 5-HT4 receptors work through stimulating the production of the neurotransmitters acetylcholine and calcitonin gene-related peptide, which enhances the spread of stimuli around and through the gut wall, to ultimately enhance and maintain a normal gut motility [77,78].…”

Section: Gastrointestinal Inflammation and Depressionmentioning

confidence: 99%

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

Waclawiková¹,

Aidy²

2018

Preprint

View full text Add to dashboard Cite

The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.

show abstract

Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT₄agonist tegaserod

Cited by 29 publications

References 34 publications

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

Contact Info

Product

Resources

About

Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4agonist tegaserod

Cited by 29 publications

References 34 publications

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

Contact Info

Product

Resources

About

Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT₄agonist tegaserod