5-HT 7 receptors: current knowledge and future prospects

Vanhoenacker, Peter; Haegeman, Guy; Leysen, Josée E.

doi:10.1016/s0165-6147(99)01432-7

Cited by 186 publications

(122 citation statements)

References 36 publications

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“…Stimulation of the native as well as heterologously expressed 5-HT 7 receptor has been shown to cause G␣s-mediated activation of adenylyl cyclases, leading to increased cAMP production (Vanhoenacker et al, 2000). In the present study, we identified the G␣12 subunit of heterotrimeric G-protein as an additional interaction partner for the 5-HT 7 receptor.…”

Section: Discussionmentioning

confidence: 59%

5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

Kvachnina¹,

Liu²,

Dityatev³

et al. 2005

J. Neurosci.

176

220

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The neurotransmitter serotonin (5-HT) plays an important role in the regulation of multiple events in the CNS. We demonstrated recently a coupling between the 5-HT 4 receptor and the heterotrimeric G13-protein resulting in RhoA-dependent neurite retraction and cell rounding (Ponimaskin et al., 2002). In the present study, we identified G12 as an additional G-protein that can be activated by another member of serotonin receptors, the 5-HT 7 receptor. Expression of 5-HT 7 receptor induced constitutive and agonist-dependent activation of a serum response element-mediated gene transcription through G12-mediated activation of small GTPases. In NIH3T3 cells, activation of the 5-HT 7 receptor induced filopodia formation via a Cdc42-mediated pathway correlating with RhoA-dependent cell rounding. In mouse hippocampal neurons, activation of the endogenous 5-HT 7 receptors significantly increased neurite length, whereas stimulation of 5-HT 4 receptors led to a decrease in the length and number of neurites. These data demonstrate distinct roles for 5-HT 7 R/G12 and 5-HT 4 R/G13 signaling pathways in neurite outgrowth and retraction, suggesting that serotonin plays a prominent role in regulating the neuronal cytoarchitecture in addition to its classical role as neurotransmitter.

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Section: Discussionmentioning

confidence: 59%

5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

Kvachnina¹,

Liu²,

Dityatev³

et al. 2005

J. Neurosci.

176

220

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“…Because DCs express 5-HT receptors, it is reasonable to suppose that if 5-HT signaling is inhibited by blocking specific 5-HT receptor function on DCs, there will be attenuation in immune cell activation and in subsequent inflammation. The 5-HT type 7 (5-HT 7 ) receptor is one of the most recently identified members of the 5-HT receptor family, and DCs express this receptor (34)(35)(36). In this study, we investigated 5-HT 7 receptor expression on colonic DCs and the effect of blocking 5-HT signaling in colitis by using antagonists against the 5-HT 7 receptor and 5-HT 7 receptordeficient mice with a view to develop an improved therapeutic strategy against intestinal inflammatory disorders.…”

mentioning

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

106

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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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“…The mechanisms underlying the observed attenuation of the excitatory effect of the 5-HT 7 receptor activation by SB 269970 may potentially be related to either the decreased receptor density or the modification in the capacity of the receptor to activate G protein, changes in G protein expression or phosphorylation, or modifications at the level of effectors. The data demonstrated that both single and repeated SB 269970 administration lowered the level of mRNA of those G proteins (Gas and Ga12) which couple to the 5-HT 7 receptor in the hippocampus [103]. Repeated treatment with SB 269970 also decreased the density of 5-HT 7 receptors [98].…”

Section: +mentioning

confidence: 92%

Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain

Tokarski

Bobula

Grzegorzewska-Hiczwa

et al. 2012

Pharmacological Reports

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Abstract:This paper summarizes a series of electrophysiological studies aimed at finding the effects of the activation of 5-HT 7 receptors on neuronal excitability as well as on excitatory and inhibitory synaptic transmission in the hippocampus and in the frontal cortex of the rat. These studies demonstrated that 5-HT 7 receptors play an important role in the modulation of the activity of the hippocampal network by regulating the excitability of pyramidal cells of the CA1 area, as well as via their effect on GABA and glutamatergic transmission. The reactivity of 5-HT 7 receptors in the hippocampus is decreased by repeated administration of antidepressant drugs and increased by a prolonged high level of corticosterone. More importantly, administration of antidepressant drug, imipramine, prevents the occurrence of corticosterone-induced changes in the function of hippocampal 5-HT 7 receptors. It has also been found that the blockade of 5-HT 7 receptors by the selective antagonist SB 269970, lasting for a few days, causes similar changes to those observed after long-term administration of antidepressants. Thus, it seems that the pharmacological blockade of 5-HT 7 receptors produces faster effects compared to classic antidepressant drugs. A similarity between the changes in the glutamatergic transmission induced by the blockade of 5 HT 7 receptors and those caused by repeated administration of the antidepressant drug, imipramine, has also been found in the frontal cortex. It has also been shown that the changes in glutamatergic transmission and the impairment of long-term synaptic plasticity in the frontal cortex of animals subjected to repeated restraint stress are reversed by the blockade of 5-HT 7 receptors. Overall, these studies, together with the data provided by other investigators, support the hypothesis that 5-HT 7 receptor antagonists may become a prototype of a new class of antidepressant drugs. Such compounds will not function by blocking 5-HT reuptake, as many of the currently used drugs, but through a direct interaction with the 5-HT 7 receptor. This type of action is highly selective and usually does not require the occurrence of adaptive changes in neuronal functions, thus allowing for a much quicker therapeutic effect.

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5-HT 7 receptors: current knowledge and future prospects

Cited by 186 publications

References 36 publications

5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

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

Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain

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5-HT 7 receptors: current knowledge and future prospects

Cited by 186 publications

References 36 publications

5-HT7Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

5-HT7Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

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

Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain

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Product

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5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology