The Serotonin-6 Receptor as a Novel Therapeutic Target

Yun, Hyung-Mun; Rhim, Hyewhon

doi:10.5607/en.2011.20.4.159

Cited by 64 publications

(57 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It was previously reported that 5-HT 6 R physically and functionally interacts with Jab1 and the activation of 5-HT 6 R releases Jab11324. Jab1 has been reported to interact with Smad5 and cause an attenuation of BMP-dependent transcriptional responses, suggesting that Jab1 might act as an inhibitor of BMP signaling26.…”

Section: Resultsmentioning

confidence: 98%

Peripheral serotonin-mediated system suppresses bone development and regeneration via serotonin 6 G-protein-coupled receptor

Yun

Park

Hong

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

Serotonin is important in brain functions and involved in neurological diseases. It is also drawn considerable attention in bone disease since it mainly produced by the gut. Serotonin 6 G-protein-coupled receptor (5-HT6R) is clinical targets for the treatment of neurological diseases. However, 5-HT6R as a therapeutic target in bone has not been reported. Herein, we found that 5-HT6R showed higher expression in bone, and its expression was increased during bone remodeling and osteoblast differentiation. The activation of 5-HT6R by ST1936 caused the inhibition of ALP activity and mineralization in primary osteoblast cultures, which was antagonized by SB258585, an antagonist and by the knockdown of 5-HT6R. Further investigation indicated that 5-HT6R inhibited osteoblast differentiation via Jab1 in BMP2 signaling but not PKA and ERK1/2. In vivo studies showed that the activation of 5-HT6R inhibited bone regeneration in the calvarial defect mice and also delayed bone development in newborn mice; this response was antagonized by SB258585. Therefore, our findings indicate a key role of 5-HT6R in bone formation through serotonin originating in the peripheral system, and suggest that it is a novel therapeutic target for drug development in the bone repair and bone diseases.

show abstract

Section: Resultsmentioning

confidence: 98%

Peripheral serotonin-mediated system suppresses bone development and regeneration via serotonin 6 G-protein-coupled receptor

Yun

Park

Hong

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Based on previous studies, a more likely explanation for antidepressant-like effects of 5-HT 6 receptor agonist and antagonist is that the analogous behavioral effects are mediated through different neurochemical mechanisms. 5-HT 6 receptor agonists produce antidepressant-like effects similar to those of selective serotonin reuptake inhibitors (SSRIs) through global stimulation of postsynaptic 5-HT receptors, and the effects may also involve in improvement of GABA neurotransmission, whereas the effects of 5-HT 6 receptor antagonists involve in enhancement of brain DA and NA neurotransmission (Wesolowska, 2010;Yun and Rhim, 2011).…”

Section: Discussionmentioning

confidence: 99%

Serotonin6 receptors in the dorsal hippocampus regulate depressive-like behaviors in unilateral 6-hydroxydopamine-lesioned Parkinson's rats

Liu

Tan

et al. 2015

Neuropharmacology

View full text Add to dashboard Cite

“…Furthermore, it has been documented that increased Fyn expressions would possibly induce activation of ERK1/2 to phosphorylated ERK1/2 (p-ERK1/2) through interacting with the carboxyl-terminal region of HTR6 [31,32]. ERK1/2 that was highly expressed in the central nervous system could affect the formation of MFS by modulating neurotransmitters, neurotropic factors (e.g.…”

Section: Discussionmentioning

confidence: 99%

The Role of 5-HTR6 in Mossy Fiber Sprouting: Activating Fyn and p-ERK1/2 in Pilocarpine-Induced Chronic Epileptic Rats

Lin

Huang

Chen

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Objective: Our primary objective is to verify whether 5-HTR6 is involved in the development of mossy fiber sprouting (MFS), and to determine how the progression of MFS is affected by 5-HTR6. Methods: A total of 90 male adult Sprague-Dawley rats were allocated into either the control group (n=36) or the epileptic group (n=54). Status epilepticus (SE) of rats was induced by the intraperitoneal (i.p.) injection of LiCl-pilocarpine. We conducted our experiments in two stages. The first stage involves equally dividing 36 epileptic rats into three groups with treatments of none, 5-HTR6 antagonist SB-27104 (SB) and vehicle DMSO. Then behavior and electroencephalogram (EEG) of rats were monitored by video-EEG. The second stage involves dividing 126 epileptic rats into seven groups with treatments of none, 10% DMSO, SB (100 µg/kg), Fyn antagonist PP 2 (50 µg/kg), p-ERK1/2 antagonist PD-98059 (30 µg/kg), SB (100 µg/ kg) + PP 2 (50 µg/kg); SB (100 µg/kg) + PD-98059 (30 µg/kg). We also treated 18 rats in the control group of the first stage with 100 µg/kg 5-HTR6 agonist WAY-181187 (WAY). MFS of rats was detected through the approach of Timm's staining. Finally, expressions of 5-HTR6, Fyn, p-ERK1/2 and GAP-3 were qualified and semi-quantified via western blotting or RT-PCR. Results: Induction of SE could stimulate formation of MFS and increased GAP-43 expressions. Expressions of 5-HTR6, Fyn and p-ERK1/2 were also up-regulated with increasing time after establishment of SE models. The development of MFS was remarkably inhibited by SB, PP 2 and PD. Compared to the single antagonist, such an inhibitory effect was enhanced by SB+PD or SB+PP. Moreover, treatment of healthy rats with WAY would contribute to up-regulated Fyn and p-ERK1/2 expressions, as well as development of MFS (P < 0.05). Suppression of Fyn triggered a down-regulating trend of p-ERK1/2 (P < 0.05), however, suppressed p-ERK1/2 did not have such a significant effect on Fyn expression. Conclusion: HTR6 may affect the progression of MFS by activating both p-ERK1/2 and Fyn, which further modulate the expression of GAP-43.W. Lin and W. Huang contributed equally to this work.

show abstract

The Serotonin-6 Receptor as a Novel Therapeutic Target

Cited by 64 publications

References 67 publications

Peripheral serotonin-mediated system suppresses bone development and regeneration via serotonin 6 G-protein-coupled receptor

Peripheral serotonin-mediated system suppresses bone development and regeneration via serotonin 6 G-protein-coupled receptor

Serotonin6 receptors in the dorsal hippocampus regulate depressive-like behaviors in unilateral 6-hydroxydopamine-lesioned Parkinson's rats

The Role of 5-HTR6 in Mossy Fiber Sprouting: Activating Fyn and p-ERK1/2 in Pilocarpine-Induced Chronic Epileptic Rats

Contact Info

Product

Resources

About