Serotonin receptor modulators in the treatment of irritable bowel syndrome

Fayyaz, Mohammad; Lackner, Jeffrey M.

doi:10.2147/tcrm.s140

Cited by 35 publications

(9 citation statements)

References 77 publications

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“…It was notable that three individuals reported here with MMIHS due to apparent de novo mutations in ACTG2 reported clinical improvement on cisapride, a serotonergic 5HT 4 agonist. Serotonergic activity at the 5HT 4 receptor has been noted to be a therapeutic target for constipation and irritable bowel syndrome [38] . Cisapride was proposed as a therapy for MMIHS in 1991 [14] .…”

Section: Discussionmentioning

confidence: 99%

Heterozygous De Novo and Inherited Mutations in the Smooth Muscle Actin (ACTG2) Gene Underlie Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome

et al. 2014

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Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare disorder of enteric smooth muscle function affecting the intestine and bladder. Patients with this severe phenotype are dependent on total parenteral nutrition and urinary catheterization. The cause of this syndrome has remained a mystery since Berdon's initial description in 1976. No genes have been clearly linked to MMIHS. We used whole-exome sequencing for gene discovery followed by targeted Sanger sequencing in a cohort of patients with MMIHS and intestinal pseudo-obstruction. We identified heterozygous ACTG2 missense variants in 15 unrelated subjects, ten being apparent de novo mutations. Ten unique variants were detected, of which six affected CpG dinucleotides and resulted in missense mutations at arginine residues, perhaps related to biased usage of CpG containing codons within actin genes. We also found some of the same heterozygous mutations that we observed as apparent de novo mutations in MMIHS segregating in families with intestinal pseudo-obstruction, suggesting that ACTG2 is responsible for a spectrum of smooth muscle disease. ACTG2 encodes γ2 enteric actin and is the first gene to be clearly associated with MMIHS, suggesting an important role for contractile proteins in enteric smooth muscle disease.

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Section: Discussionmentioning

confidence: 99%

Heterozygous De Novo and Inherited Mutations in the Smooth Muscle Actin (ACTG2) Gene Underlie Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome

et al. 2014

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“…Additionally, about 95% of the serotonin in the body is found in the GI tract. Colonic distention results in the secretion of serotonin by enterochromaffin cells, which will induce nausea and vomiting [12]. For this reason, we propose the use of 5 HT-3 receptor antagonists for the prevention of vomiting due to colonic distention, especially for patients with risk factors for postoperative nausea and vomiting [13].…”

Section: Discussionmentioning

confidence: 99%

Explosive Vomiting Associated with Proximal Colonic Distention during a Difficult Propofol-Assisted Colonoscopy

Rah

Ferges²,

Tse

2019

Case Reports in Anesthesiology

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We present a case of explosive vomiting associated with the extensive manipulation of the proximal colon during a difficult colonoscopy procedure. The cause of vomiting in this case may have been multifactorial; however, proximal colonic distention was the most likely factor because the onset of vomiting coincided with proximal colonic manipulation and happened without any prodromal signs, coughing, and airway obstruction. Propofol, the sedative most commonly administered to the patient during colonoscopy, allows for a deep state of sedation, and consequently extensive colonic distention and scope manipulation. Colonic distention may lead to a higher risk of vomiting. We reviewed the neurocircuitry associated with vomiting and discussed why proximal colonic distention may increase the risk of vomiting. We emphasize vigilance during the manipulation of the proximal colon because vomiting increases the potential for aspiration pneumonitis and pneumonia in patients under deep propofol sedation with attenuated airway responses.

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“…Patients diagnosed with IBS or other bowel diseases show high levels of 5-HT and an increased frequency of T H17 cells. In fact, both 5-HTR agonists and antagonists have been used to treat IBS that also helped with other related symptoms ( 213 ). 5-HT 3 , 5-HT 4 , and 5HT 1B are the most important receptors for GI function.…”

Section: Immunomodulatory Neurotransmittersmentioning

confidence: 99%

Critical Neurotransmitters in the Neuroimmune Network

et al. 2020

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Immune cells rely on cell-cell communication to specify and fine-tune their responses. They express an extensive network of cell communication modes, including a vast repertoire of cell surface and transmembrane receptors and ligands, membrane vesicles, junctions, ligand and voltage-gated ion channels, and transporters. During a crosstalk between the nervous system and the immune system these modes of cellular communication and the downstream signal transduction events are influenced by neurotransmitters present in the local tissue environments in an autocrine or paracrine fashion. Neurotransmitters thus influence innate and adaptive immune responses. In addition, immune cells send signals to the brain through cytokines, and are present in the brain to influence neural responses. Altered communication between the nervous and immune systems is emerging as a common feature in neurodegenerative and immunopathological diseases. Here, we present the mechanistic frameworks of immunostimulatory and immunosuppressive effects critical neurotransmitters-dopamine (3,4-dihydroxyphenethylamine), serotonin (5hydroxytryptamine), substance P (trifluoroacetate salt powder), and L-glutamateexert on lymphocytes and non-lymphoid immune cells. Furthermore, we discuss the possible roles neurotransmitter-driven neuroimmune networks play in the pathogenesis of neurodegenerative disorders, autoimmune diseases, cancer, and outline potential clinical implications of balancing neuroimmune crosstalk by therapeutic modulation.

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Serotonin receptor modulators in the treatment of irritable bowel syndrome

Cited by 35 publications

References 77 publications

Heterozygous De Novo and Inherited Mutations in the Smooth Muscle Actin (ACTG2) Gene Underlie Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome

Heterozygous De Novo and Inherited Mutations in the Smooth Muscle Actin (ACTG2) Gene Underlie Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome

Explosive Vomiting Associated with Proximal Colonic Distention during a Difficult Propofol-Assisted Colonoscopy

Critical Neurotransmitters in the Neuroimmune Network

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