Comparison of 5-HT4 and 5-HT7 receptor expression and function in the circular muscle of the human colon

Irving, Helen Ruth; Tan, Yean Yeow; Tochon-Danguy, Nathalie; Liu, Haihuang; Chetty, Navinisha; Desmond, Paul; Pouton, Colin W.; Coupar, Ian M.

doi:10.1016/j.lfs.2006.12.025

Cited by 33 publications

(37 citation statements)

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“…This indicates the involvement of 5-HT 7 receptors in a relaxation response to the endogenous 5-HT as antagonism of these receptors resulted in a greater response. This is in line with previous studies where the 5-HT 7 receptor was implicated in a relaxation response in the gastrointestinal tract (45)(46)(47). In summary, the application of 5-HT receptor antagonists, revealed that methysergide-(5-HT1/2/7 receptor), ritanserin-(5-HT 2 receptor), SB258585-(5-HT 6 receptor) and SB269970-(5-HT 7 receptor) sensitive sites might be involved in the endogenous 5-HT mediating contraction or relaxation response to EFS.…”

Section: Discussionsupporting

confidence: 93%

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

2014

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Background:The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT 1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT 4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT 6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT 7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions:The application of 5-HT 1A , 5-HT 2 , 5-HT 3 , 5-HT 4 , 5-HT 6 and 5-HT 7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions.

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Section: Discussionsupporting

confidence: 93%

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

2014

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“…The distribution of 5-HT 3 receptor A subunits is in keeping with previous studies where this subunit was widespread and thought to reflect the distribution of functional 5-HT 3 receptor subunits. 11,22,23,25,48 The HTR3B gene which encodes for the canonical 5-HT 3 receptor B subunit was expressed at lower levels than HTR3A in all regions of colon but at similar levels in the ileum (Fig. 1).…”

Section: Discussionmentioning

confidence: 97%

“…Since several splice variants with overlapping 3' coding regions exist for the 5-HT 4 and 5-HT 7 receptors, their distribution was examined us- ing partial or nested PCR. GAPDH expression was used as a control for this analysis as it has previously been shown to be comparable between human colonic tissue layers 11 ( Fig. 1 and Supplementary Fig.…”

Section: Distribution Of 5-ht 4 and 5-ht 7 Receptors In The Human Intmentioning

confidence: 99%

“…[1][2][3][4][5] Inflammation contributes to these disorders due to underlying inflammatory states in coeliac disease and inflammatory bowel disease and in part because it modulates serotonin levels. 1,4,6 The serotonin (5-HT) 4 receptor is expressed in several different cell types in the human colon [7][8][9][10][11][12][13][14][15][16] where it stimulates intestinal activity (ie, prokinetic action) and is a target for treating constipation predominant IBS (IBS-C) and chronic constipation. The 5-HT 4 receptor partial agonist, tegaserod was used for treatment of IBS-C until withdrawn in 2007 as it was associated with rare adverse cardiovascular effects.…”

Section: Introductionmentioning

confidence: 99%

“…17 Intestinal 5-HT 7 receptors are often located near 5-HT 4 receptors where they augment 5-HT induced responses. 11,18 5-HT 3 receptor antagonists decrease colonic motility, secretion and nociception and are used to treat diarrhea predominant IBS (IBS-D). 1,3 The 5-HT 3 receptor is a ligand gated ion channel composed of 5 subunits that form homomeric (all 3A subunits) or heteromeric (mixture of 3A and 3B, 3C, 3D, or 3E subunits) functionally active channels.…”

Section: Introductionmentioning

confidence: 99%

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Distribution of 5-HT₃, 5-HT₄, and 5-HT₇Receptors Along the Human Colon

Yaakob

Chinkwo

Chetty

et al. 2015

J Neurogastroenterol Motil

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Background/AimsSeveral disorders of the gastrointestinal tract are associated with abnormal serotonin (5-HT) signaling or metabolism where the 5-HT 3 and 5-HT 4 receptors are clinically relevant. The aim was to examine the distribution of 5-HT 3 , 5-HT 4 , and 5-HT 7 receptors in the normal human colon and how this is associated with receptor interacting chaperone 3, G protein coupled receptor kinases, and protein LIN-7 homologs to extend previous observations limited to the sigmoid colon or the upper intestine. MethodsSamples from ascending, transverse, descending, and sigmoid human colon were dissected into 3 separate layers (mucosa, longitudinal, and circular muscles) and ileum samples were dissected into mucosa and muscle layers (n = 20). Complementary DNA was synthesized by reverse transcription from extracted RNA and expression was determined by quantitative or end point polymerase chain reaction. ResultsThe 5-HT3 receptor subunits were found in all tissues throughout the colon and ileum. The A subunit was detected in all samples and the C subunit was expressed at similar levels while the B subunit was expressed at lower levels and less frequently. The 5-HT3 receptor E subunit was mainly found in the mucosa layers. All splice variants of the 5-HT4 and 5-HT7 receptors were expressed throughout the colon although the 5-HT4 receptor d, g, and i variants were expressed less often. ConclusionsThe major differences in 5-HT receptor distribution within the human colon are in relation to the mucosa and muscular tissue layers where the 5-HT 3 receptor E subunit is predominantly found in the mucosal layer which may be of therapeutic relevance.

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Serotonin Modulation of Macrophage Polarization: Inflammation and Beyond

Casas-Engel

Corbí

2014

Advances in Experimental Medicine and Biology

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Macrophages display a ample plethora of effector functions whose acquisition is promoted by the surrounding cytokine and cellular environment. Depending on the stimulus, macrophages become specialized ("polarized") for either pathogen elimination, tissue repair and wound healing or immunosuppression. This "polarization" versatility allows macrophages to critically contribute to tissue homeostasis, as they promote initiation and resolution of inflammatory responses. As a consequence, deregulation of the tissue macrophage polarization balance is an etiological agent of chronic inflammation, autoimmune diseases, cancer and even obesity and insulin resistance. In the present review we describe current concepts on the molecular basis and the patho-physiological implications of macrophage polarization, and describe its modulation by serotonin (5-HT), a neurotransmitter that regulates inflammation and tissue repair via a large set of receptors (5-HTR1-7). 5-HT modulates the phenotypic and functional polarization of macrophages, and contributes to the maintenance of an anti-inflammatory state mainly via 5-HTR2B and 5-HTR7, whose activation has a great impact on macrophage gene expression profile. The identification of 5-HTR2B and 5-HTR7 as functionally-relevant polarization markers suggests their therapeutic value in inflammatory pathologies as well as their potential involvement in linking the immune and nervous systems.

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Comparison of 5-HT4 and 5-HT7 receptor expression and function in the circular muscle of the human colon

Cited by 33 publications

References 36 publications

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Distribution of 5-HT₃, 5-HT₄, and 5-HT₇Receptors Along the Human Colon

Serotonin Modulation of Macrophage Polarization: Inflammation and Beyond

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Comparison of 5-HT4 and 5-HT7 receptor expression and function in the circular muscle of the human colon

Cited by 33 publications

References 36 publications

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Distribution of 5-HT3, 5-HT4, and 5-HT7Receptors Along the Human Colon

Serotonin Modulation of Macrophage Polarization: Inflammation and Beyond

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Distribution of 5-HT₃, 5-HT₄, and 5-HT₇Receptors Along the Human Colon