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

Dickson, Eamonn J.; Heredia, Dante J.; Smith, Terence K.

doi:10.1152/ajpgi.00496.2009

Cited by 61 publications

(147 citation statements)

References 45 publications

(144 reference statements)

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“…Recently, a 5-HT 1A receptor agonist has been shown to increase esophageal motility and colonic migrating motor complexes (14,15). Accordingly, we speculate that the prokinetic effects of mirtazapine observed in this study are attributed to increased release of 5-HT (mainly via the actions of 5-HT 2C and 5-HT 1A ) and the blockage of ␣ 2 adrenergic receptors.…”

Section: Discussionsupporting

confidence: 54%

Prokinetic effects of mirtazapine on gastrointestinal transit

Yin

Song

Lei

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Mirtazapine is a noradrenergic and specific serotonergic antidepressant. The aim of this study was to investigate the effects of mirtazapine on gastrointestinal motility in dogs, including solid gastric emptying, antral and small intestinal contractions, and small intestinal and colonic transit. Six dogs were implanted with two cannulas located at the duodenum and the ascending colon; another six dogs were implanted with gastric cannula 6 cm proximal to the pylorus. Mirtazapine 45 mg was administered orally 90 min before the study. We found that 1) Mirtazapine accelerated gastric emptying during the entire 3 h in normal dogs (P Ͻ 0.04) and accelerated delayed gastric emptying induced by rectal distention (P Ͻ 0.04). 2) Mirtazapine restored impaired gastric tone and accommodation induced by rectal distention (P Ͻ 0.05). 3) No significant changes were noted in small intestinal contractions or transit with mirtazapine (P Ͼ 0

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Section: Discussionsupporting

confidence: 54%

Prokinetic effects of mirtazapine on gastrointestinal transit

Yin

Song

Lei

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…(1) Colonic migrating motor complexes (CMMCs) 8 (2) Tonic inhibition of the muscle 21 (3) Secretomotor activity and blood flow 14,22 CMMCs and high amplitude propagating contractions (HAPCs) are probably a similar integrated motor events ( Fig. 2A and 2B) normally involving both mucosal 5-HT and myenteric 5-HT neurons.…”

Section: Introductionmentioning

confidence: 99%

“…8,[23][24][25] Some 5-HT neurons, which may also release acetylcholine (ACh), appear to be spontaneously active and contribute to tonic inhibition of the muscle and pacemaker ICC between CMMCs. 21 5-HT neurons are also necessary for CMMC propagation and generation. 21 During the CMMC, there is a defined pattern switch that turns off IMNs to allow full excitation of the muscle and pacemaker ICC by EMNs.…”

Section: Introductionmentioning

confidence: 99%

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

Smith

Park

Hennig

2014

J Neurogastroenterol Motil

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The colonic migrating motor complex (CMMC) is a critical neurally mediated rhythmic propulsive contraction observed in the large intestine of many mammals. It seems to be equivalent to the high amplitude propagating contractions (HAPCs) in humans. This review focuses on the probable neural mechanisms involved in producing the CMMC or HAPC, their likely dependence on mucosal and neuronal serotonin and pacemaker insterstitial cells of Cajal networks and how intrinsic neural reflexes affect them. Discussed is the possibility that myenteric 5-hydroxytryptamine (5-HT) neurons are not only involved in tonic inhibition of the colon, but are also involved in generating the CMMC and modulation of the entire enteric nervous system, including coupling motility to secretion and blood flow. Mucosal 5-HT appears to be important for the initiation and effective propagation of CMMCs, although this mechanism is a longstanding controversy since the 1950s, which we will address. We argue that the slow apparent propagation of the CMMC/HAPC down the colon is unlikely to result from a slowly conducting wave front of neural activity, but more likely because of an interaction between ascending excitatory and descending (serotonergic) inhibitory neural pathways interacting both within the myenteric plexus and at the level of the muscle. That is, CMMC/HAPC propagation appears to be similar to esophageal peristalsis. The suppression of inhibitory (neuronal nitric oxide synthase) motor neurons and mucosal 5-HT release by an upregulation of prostaglandins has important implications in a number of gastrointestinal disorders, especially slow transit constipation.

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“…Second, the effect was not affected by (S)-WAY 100135, which rules out the involvement of 5-HT1A receptors. The exact role of these receptors in the control of colonic motility is still enigmatic [72], but recent findings suggest that these receptors take part in the modulation of colonic migrating motor complex by limiting the neurotransmitter output from intrinsic primary afferent neurons (IPANs) to ascending (S Type I) interneurons [31]. Our results suggest that 5-HT1A receptors are not involved in the inhibition of cholinergic contractions in the murine colon.…”

Section: It Is Well-established That Peptic Ulcers Develop As a Resumentioning

confidence: 62%

“…5HT1A receptors have been implicated in numerous GI processes, such as gastric mucosal protection [27,28], inhibition of cholinergic gastric contractions [29,30], as well as modulation of colonic motility [31]. It should be emphasized that ulcer disease is often accompanied by increased gastric motility [32], consequently inhibition of GI motility may contribute to the therapeutic effect of an antiulcer agent.…”

Section: Introductionmentioning

confidence: 99%

Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility

et al. 2016

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Background. Allyphenyline, a novel α2-adrenoceptor (AR) ligand has been shown to selectively activate α2C-adrenoceptors (AR) and 5HT1A receptors, but also to behave as a neutral antagonist of α2A-ARs. We exploited this unique pharmacological profile to analyze the role of α2C-ARs and 5HT1A receptors in the regulation of gastric mucosal integrity and gastrointestinal motility. Methods. Similar inhibition was observed in the colon, however, in this case only ARC 239 reduced this effect, while neither selective inhibition of α2C-ARs and 5HT1A receptors, nor genetic deletion of α2A-and α2B-ARs influenced it. Conclusions. Activation of both central α2C-ARs and 5HT1A receptors contributes to the gastroprotective action of allyphenyline in rats. Its inhibitory effect on fundic contractions is mediated by 5HT1A receptors, but neither α2-ARs, nor 5HT1A receptors take part in its inhibitory effect on colonic contractility in mice.

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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

Cited by 61 publications

References 45 publications

Prokinetic effects of mirtazapine on gastrointestinal transit

Prokinetic effects of mirtazapine on gastrointestinal transit

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

Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility

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