Evidence for 5‐HT<sub>7</sub> receptors mediating relaxation of human colonic circular smooth muscle

Prins, Nicolaas H.; Briejer, M.R.; Bergen, Patrick J E Van; Akkermans, L.M.A.; Schuurkes, J. A. J.

doi:10.1038/sj.bjp.0702762

Cited by 79 publications

(72 citation statements)

References 10 publications

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“…In the gut, studies have shown that 5-HT induces muscle relaxation by affecting 5-HT 7 receptors on smooth muscle cells in addition to neuronal 5-HT 7 receptors (55)(56)(57)(58). Although the effects of selective 5-HT 7 antagonism have been studied in several animal behavioral models where it has been shown to have anxiolytic (59-61), antidepressant (62)(63)(64), and antipsychotic-like effects (65,66), to our knowledge, no current data are available on the effects of 5-HT 7 receptor antagonists in IBD.…”

Section: Cd11cmentioning

confidence: 99%

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Kim

Bridle

Ghia

et al. 2013

The Journal of Immunology

111

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Mucosal inflammation in conditions ranging from infective acute enteritis or colitis to inflammatory bowel disease is accompanied by alteration in serotonin (5-hydroxytryptamine [5-HT]) content in the gut. Recently, we have identified an important role of 5-HT in the pathogenesis of experimental colitis. 5-HT type 7 (5-HT7) receptor is one of the most recently identified members of the 5-HT receptor family, and dendritic cells express this receptor. In this study, we investigated the effect of blocking 5-HT7 receptor signaling in experimental colitis with a view to develop an improved therapeutic strategy in intestinal inflammatory disorders. Colitis was induced with dextran sulfate sodium (DSS) or dinitrobenzene sulfonic acid (DNBS) in mice treated with selective 5-HT7 receptor antagonist SB-269970, as well as in mice lacking 5-HT7 receptor (5-HT7−/−) and irradiated wild-type mice reconstituted with bone marrow cells harvested from 5-HT7−/− mice. Inhibition of 5-HT7 receptor signaling with SB-269970 ameliorated both acute and chronic colitis induced by DSS. Treatment with SB-269970 resulted in lower clinical disease, histological damage, and proinflammatory cytokine levels compared with vehicle-treated mice post-DSS. Colitis severity was significantly lower in 5-HT7−/− mice and in mice reconstituted with bone marrow cells from 5-HT7−/− mice compared with control mice after DSS colitis. 5-HT7−/− mice also had significantly reduced DNBS-induced colitis. These observations provide us with novel information on the critical role of the 5-HT7 receptor in immune response and inflammation in the gut, and highlight the potential benefit of targeting this receptor to alleviate the severity of intestinal inflammatory disorders such as inflammatory bowel disease.

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Section: Cd11cmentioning

confidence: 99%

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Kim

Bridle

Ghia

et al. 2013

The Journal of Immunology

111

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“…This 5-HT 7 receptor population is considered to be 'atypical', because the rat jejunum is the only peripheral tissue where stimulation of 5-HT 7 receptors leads to contraction [2]. In contrast, other smooth muscle preparations, such as the guinea pig ileum [3] and human colonic circular smooth muscle [4], are relaxed. The 5-HT 7 receptor is positively coupled to adenylyl cyclase [5] and in smooth muscle the subsequent elevation of cyclic AMP is generally agreed to cause relaxation [6,7].…”

Section: Introductionmentioning

confidence: 99%

Influences of Gender and Region on Responses to 5-HT in the Rat Small Intestine

et al. 2004

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The aim of this study was to obtain more information regarding the ‘atypical’ 5-HT₇ receptor of the rat jejunum. 5-HT₇-induced contractions of the jejunum were elicited by 5-HT in the presence of ondansetron. Maximal responses were slightly larger in tissues from male compared to female rats of comparable age, with E_max values of 97.2 ± 3.3 and 84.25 ± 4.3% respectively compared to acetylcholine as an internal standard. However, the pEC₅₀valuesfor 5-HT were not significantly different. The mRNA expression levels of the 5-HT₇receptor were similar in whole jejunum and longitudinal muscle tissues taken from males and females. It was also shown that the maximal response of the jejunum from male rats was larger than the responses from mid intestine and ileum. However, in female tissues, the E_max of the mid intestine was significantly larger than the ileum, but not different from the jejunum. The results provide further insights into the ‘atypical’ 5-HT₇ receptor of the rat jejunum and are also useful in optimising the preparation for further studies.

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“…In the periphery, studies have mainly concentrated on vascular and alimentary tract tissues showing that relaxation of smooth muscle is mediated by the 5-HT 7 receptor. These include porcine vena cava [5] and myometrium [6], guinea-pig ileum [7] and human colonic circular smooth muscle [8]. The exception is the rat small intestine, which to our knowledge, is the only peripheral tissue where stimulation of the 5-HT 7 receptor leads to contraction [9].…”

Section: Introductionmentioning

confidence: 99%

Effects of Some Antidepressant Drugs on Tryptaminergic Responses of the Rat Jejunum

Liu¹,

Coupar²,

Irving³

2003

Pharmacology

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The rat isolated jejunum was used as a functional model to screen some antidepressant drugs at the ‘atypical’ 5-HT₇ receptor. Mianserin acted as a surmountable antagonist of 5-CT with a pA₂ value of 8.22 ± 0.33. The apparent pK_B of maprotiline against 5-CT was 7.67 ± 0.24 at 100 nmol/l, but higher concentrations suppressed the maxima. An apparent pK_B could not be obtained for amitriptyline, because 10 nmol/l reduced the E_max of 5-CT without causing parallel displacement. Higher concentrations of 30 and 100 nmol/l caused further suppressions. Amoxapine, loxapine and desipramine (each at 100 nmol/l) caused similar effects, suppressing the E_max values to 5-HT by approximately 50%, while lower concentrations failed to cause parallel displacements. These results further extend the activity profiles of the drugs investigated.

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Evidence for 5‐HT₇ receptors mediating relaxation of human colonic circular smooth muscle

Cited by 79 publications

References 10 publications

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Influences of Gender and Region on Responses to 5-HT in the Rat Small Intestine

Effects of Some Antidepressant Drugs on Tryptaminergic Responses of the Rat Jejunum

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Evidence for 5‐HT7 receptors mediating relaxation of human colonic circular smooth muscle

Cited by 79 publications

References 10 publications

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Influences of Gender and Region on Responses to 5-HT in the Rat Small Intestine

Effects of Some Antidepressant Drugs on Tryptaminergic Responses of the Rat Jejunum

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Evidence for 5‐HT₇ receptors mediating relaxation of human colonic circular smooth muscle