Chronotropic action of 5-hydroxytryptamine (5-HT) on colonic migrating motor complexes (CMMCs) in the isolated mouse colon

Fida, Rosa; Bywater, Robert A.R.; Lyster, D. J. K.; Taylor, Grahame S.

doi:10.1016/s0165-1838(00)00074-6

Cited by 26 publications

(34 citation statements)

References 32 publications

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“…Previously it has been shown that ondansetron and alosetron block spontaneous CMMCs generated in isolated flaccid tubes of murine colon (3,10). We have recently shown that, in addition to ondansetron, spontaneous CMMCs are also abolished by removing the mucosa (1, 8, 18).…”

Section: Role Of 5-ht 3 Receptors In Generating Tonic Inhibition and mentioning

confidence: 97%

“…A number of gut inflammatory and constipatory conditions involve altered levels of serotonin and signaling, in part brought about by altered numbers of EC cells and 5-HT-containing neurons (15, 16). There are numerous 5-HT receptors in the gut, and there is much interest in developing antagonists and agonists to these receptors, especially 5-HT 3 and 5-HT 4 receptors, to treat a variety of gastrointestinal conditions (10,16,19,27,31,33).The circular muscle (CM) of the large bowel is under constant tonic neural inhibition, which keeps the muscle in a hyperpolarized state (1,4,8,26,38). Tonic inhibition appears to be necessary for normal pellet transit and stool formation in the murine colon (8).…”

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Critical role of 5-HT_1A, 5-HT₃, and 5-HT₇ receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex

Dickson

Heredia

Smith

2010

American Journal of Physiology-Gastrointestinal and Liver Physi

140

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Dickson EJ, Heredia DJ, Smith TK. Critical role of 5-HT1A, 5-HT 3, and 5-HT7 receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex. Am J Physiol Gastrointest Liver Physiol 299: G144 -G157, 2010. First published April 22, 2010; doi:10.1152/ajpgi.00496.2009.-The colonic migrating motor complex (CMMC) is necessary for fecal pellet propulsion in the murine colon. We have previously shown that 5-hydroxytryptamine (5-HT) released from enterochromaffin cells activates 5-HT 3 receptors on the mucosal processes of myenteric Dogiel type II neurons to initiate the events underlying the CMMC. Our aims were to further investigate the roles of 5-HT 1A, 5-HT3, and 5-HT 7 receptor subtypes in generating and propagating the CMMC using intracellular microelectrodes or tension recordings from the circular muscle (CM) in preparations with and without the mucosa. Spontaneous CMMCs were recorded from the CM in isolated murine colons but not in preparations without the mucosa. In mucosaless preparations, ondansetron (3 M; 5-HT 3 antagonist) plus hexamethonium (100 M) completely blocked spontaneous inhibitory junction potentials, depolarized the CM. Ondansetron blocked the preceding hyperpolarization associated with a CMMC. Spontaneous CMMCs and CMMCs evoked by spritzing 5-HT (10 and 100 M) or nerve stimulation in preparations without the mucosa were blocked by SB 258719 or SB 269970 (1-5 M; 5-HT 7 antagonists). Both and (S)-WAY100135 (1-5 M; 5-HT 1A antagonists) blocked spontaneous CMMCs and neurally evoked CMMCs in preparations without the mucosa. Both NAN-190 and (S)-WAY100135 caused an atropine-sensitive depolarization of the CM. The precursor of 5-HT, 5-hydroxytryptophan (5-HTP) (10 M), and 5-carboxamidotryptamine (5-CT) (5 M; 5-HT 1/5/7 agonist) increased the frequency of spontaneous CMMCs. 5-HTP and 5-CT also induced CMMCs in preparations with and without the mucosa, which were blocked by SB 258719. 5-HT1A, 5-HT3, and 5-HT7 receptors, most likely on Dogiel Type II/AH neurons, are important in initiating, generating, and propagating the CMMC. Tonic inhibition of the CM appears to be driven by ongoing activity in descending serotonergic interneurons; by activating 5-HT7 receptors on AH neurons these interneurons also contribute to the generation of the CMMC.5-hydroxytryptamine; AH neurons; cholinergic transmission; circular muscle; enterochromaffin cells; mucosa; serotonergic transmission; smooth muscle OVER 95% OF THE SEROTONIN IN THE BODY, also called 5-hydroxytryptamine (5-HT), resides in the gastrointestinal tract, where it plays an important role in regulating gut motility, secretion, sensation, and bone metabolism (6,15,16,45,46). Most of this 5-HT is in enterochromaffin (EC) cells in the mucosa although it is also present in a small population (ϳ1%) of descending myenteric interneurons that project to the submucus plexus, suggesting they may modulate secretomotor reflexes. Secretomotor reflexes and motility reflexes can be activated by 5-HT release from EC cells (5,6...

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Section: Role Of 5-ht 3 Receptors In Generating Tonic Inhibition and mentioning

confidence: 97%

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confidence: 99%

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confidence: 99%

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Critical role of 5-HT_1A, 5-HT₃, and 5-HT₇ receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex

Dickson

Heredia

Smith

2010

American Journal of Physiology-Gastrointestinal and Liver Physi

140

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“…Cyproheptadine was found to block the 5-HT2 receptor, resulting in decreasing contraction of longitudinal smooth muscles of small intestine in mice. 58 Another animal study in rats demonstrated that cyproheptadine also has a direct effect on the inhibition of electrogenic ionic secretion in intestinal epithelium. 59 There have been no studies demonstrating a direct effect of cyproheptadine use in the treatment of IBS in humans; however, a recent study by Madani et al 10 reported, for the first time, a complete resolution of symptoms FEATURE ARTICLE in 10 of 10 children suffering from IBS treated with cyproheptadine.…”

Section: Irritable Bowel Syndromementioning

confidence: 99%

Cyproheptadine: A Potentially Effective Treatment for Functional Gastrointestinal Disorders in Children

Krasaelap¹,

Madani²

2017

Pediatr Ann

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Functional gastrointestinal disorders (FGIDs) negatively affect children's quality of life and health care costs. It has been proposed that alteration of gut serotonin leads to gastrointestinal dysmotility, visceral hypersensitivity, altered gastrointestinal secretions, and brain-gut dysfunction. Cyproheptadine, a serotonin antagonist, has been shown to be a potentially effective and safe treatment option in children who meet the clinical criteria for FGIDs. Well-designed multicenter trials with long-term follow-up are needed to further investigate its efficacy. [Pediatr Ann. 2017;46(3):e120-e125.]

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“…Most of what we know about the possible involvement of 5-HT and the intricate mechanisms and underlying the generation and propagation of motor complexes in the large bowel largely come from studies in the isolated murine colon, 21,25,[64][65][66]94,95 although earlier studies in the feline and canine colon have contributed significantly to our understanding. 59,60,67 There appear to be notable similarities between HAPCs in the human colon and propagating motor complexes observed in the other species, especially those in mice ( Fig.…”

Section: Properties Of Rhythmic Propagating Colonic Migrating Motor Cmentioning

confidence: 99%

Colonic Migrating Motor Complexes, High Amplitude Propagating Contractions, Neural Reflexes and the Importance of Neuronal and Mucosal Serotonin

Smith¹,

Park²,

Hennig³

2014

J Neurogastroenterol Motil

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Chronotropic action of 5-hydroxytryptamine (5-HT) on colonic migrating motor complexes (CMMCs) in the isolated mouse colon

Cited by 26 publications

References 32 publications

Critical role of 5-HT_1A, 5-HT₃, and 5-HT₇ receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex

Critical role of 5-HT_1A, 5-HT₃, and 5-HT₇ receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex

Cyproheptadine: A Potentially Effective Treatment for Functional Gastrointestinal Disorders in Children

Colonic Migrating Motor Complexes, High Amplitude Propagating Contractions, Neural Reflexes and the Importance of Neuronal and Mucosal Serotonin

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Chronotropic action of 5-hydroxytryptamine (5-HT) on colonic migrating motor complexes (CMMCs) in the isolated mouse colon

Cited by 26 publications

References 32 publications

Critical role of 5-HT1A, 5-HT3, and 5-HT7 receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex

Critical role of 5-HT1A, 5-HT3, and 5-HT7 receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex

Cyproheptadine: A Potentially Effective Treatment for Functional Gastrointestinal Disorders in Children

Colonic Migrating Motor Complexes, High Amplitude Propagating Contractions, Neural Reflexes and the Importance of Neuronal and Mucosal Serotonin

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Product

Resources

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Critical role of 5-HT_1A, 5-HT₃, and 5-HT₇ receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex

Critical role of 5-HT_1A, 5-HT₃, and 5-HT₇ receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complex