Serotonin, serotonin receptors, serotonin receptor subtype agonists and pain

Pain ◽  
1990 ◽  
Vol 40 (1) ◽  
pp. 115-116 ◽  
Author(s):  
Julio Pascual
Keyword(s):  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Receptor Subtype

scholarly journals Living-Cell Diffracted X-ray Tracking Analysis Confirmed Internal Salt Bridge Is Critical for Ligand-Induced Twisting Motion of Serotonin Receptors

2021 ◽  
Vol 22 (10) ◽  
pp. 5285
Author(s):  
Kazuhiro Mio ◽  
Shoko Fujimura ◽  
Masaki Ishihara ◽  
Masahiro Kuramochi ◽  
Hiroshi Sekiguchi ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Frame Rate ◽  
Receptor Subtype ◽  
Transmembrane Segment ◽  
Hek 293 ◽  
Gold Nanocrystals ◽  
X Ray ◽  
Time Dynamics ◽  
Analytical Technique

Serotonin receptors play important roles in neuronal excitation, emotion, platelet aggregation, and vasoconstriction. The serotonin receptor subtype 2A (5-HT2AR) is a Gq-coupled GPCR, which activate phospholipase C. Although the structures and functions of 5-HT2ARs have been well studied, little has been known about their real-time dynamics. In this study, we analyzed the intramolecular motion of the 5-HT2AR in living cells using the diffracted X-ray tracking (DXT) technique. The DXT is a very precise single-molecular analytical technique, which tracks diffraction spots from the gold nanocrystals labeled on the protein surface. Trajectory analysis provides insight into protein dynamics. The 5-HT2ARs were transiently expressed in HEK 293 cells, and the gold nanocrystals were attached to the N-terminal introduced FLAG-tag via anti-FLAG antibodies. The motions were recorded with a frame rate of 100 μs per frame. A lifetime filtering technique demonstrated that the unliganded receptors contain high mobility population with clockwise twisting. This rotation was, however, abolished by either a full agonist α-methylserotonin or an inverse agonist ketanserin. Mutation analysis revealed that the “ionic lock” between the DRY motif in the third transmembrane segment and a negatively charged residue of the sixth transmembrane segment is essential for the torsional motion at the N-terminus of the receptor.

From Serotonin Receptor Classification to the Antimigraine Drug Sumatriptan

Cephalalgia ◽  
1992 ◽  
Vol 12 (4) ◽  
pp. 187-196 ◽  
Author(s):  
Pramod R Saxena ◽  
Michel D Ferrari
Keyword(s):  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Radioligand Binding ◽  
Receptor Subtype ◽  
Binding Studies ◽  
Rat Brain Membranes ◽  
Serotonin Derivatives ◽  
Parasympathetic Ganglion ◽  
Radioligand Binding Studies ◽  
New Framework

After the synthetic serotonin 5-hydroxytryptamine (5-HT) became available in the early 1950s, attempts were soon under way to study the nature of 5-HT receptors. Using the guinea-pig isolated ileum, Gaddum and Picarelli (1957) suggested that 5-HT-induced contractions were mediated by a morphine-sensitive “M” receptor located on the parasympathetic ganglion and a dibenzyline-sensitive “D” receptor located on the smooth muscle. Though this classification was used during the next three decades, it was realized that some effects of serotonin, for example vasoconstriction within the carotid vascular bed, were not mediated by either “M” or “D” receptors. When radioligand binding studies led to the identification of 5-HT1 and 5-HT2 “receptors” in the rat brain membranes, it became increasingly apparent that the two receptor classifications were not identical. Thus, a new framework for serotonin receptor nomenclature and classification was proposed: 5-HT 1 -like (5-HT 1), 5-HT 2 (formerly “D”) and 5-HT 3 (formerly “M”) receptors. At the present time, several subtypes of 5-HT 1 receptors as well as a 5-HT 4 receptor are also recognized. As the serotonin receptor classification was emerging to indicate that carotid vasoconstriction by serotonin is mediated by a subtype of 5-HT 1 receptors, on the migraine front it was being suggested that the disease is associated with vasodilatation within the cranial extracerebral circulation and deranged serotonin metabolism and that certain antimigraine drugs caused a selective carotid vasoconstriction, probably via serotonin receptors. Therefore, Humphrey and colleagues conceived that synthesis of serotonin derivatives may lead to a compound that would elicit highly selective carotid vasoconstriction and abort migraine attacks. Indeed, via the synthesis of 5-carboxamidotryptamine and AH25086, sumatriptan was designed. The drug acts as an agonist at the vasoconstrictor 5-HT 1 receptor subtype and has proved highly effective in the therapy of migraine attacks.

scholarly journals Modulation of Serotonin Receptors in Neurodevelopmental Disorders: Focus on 5-HT7 Receptor

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3348
Author(s):  
Jieon Lee ◽  
Diana Avramets ◽  
Byungsun Jeon ◽  
Hyunah Choo
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorders ◽  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Fragile X ◽  
Autism Spectrum ◽  
Neuronal Morphology ◽  
Point Of View ◽  
Receptor Subtype ◽  
Potential Therapeutic Target

Since neurodevelopmental disorders (NDDs) influence more than 3% of children worldwide, there has been intense investigation to understand the etiology of disorders and develop treatments. Although there are drugs such as aripiprazole, risperidone, and lurasidone, these medications are not cures for the disorders and can only help people feel better or alleviate their symptoms. Thus, it is required to discover therapeutic targets in order to find the ultimate treatments of neurodevelopmental disorders. It is suggested that abnormal neuronal morphology in the neurodevelopment process is a main cause of NDDs, in which the serotonergic system is emerging as playing a crucial role. From this point of view, we noticed the correlation between serotonin receptor subtype 7 (5-HT7R) and NDDs including autism spectrum disorder (ASD), fragile X syndrome (FXS), and Rett syndrome (RTT). 5-HT7R modulators improved altered behaviors in animal models and also affected neuronal morphology via the 5-HT7R/G12 signaling pathway. Through the investigation of recent studies, it is suggested that 5-HT7R could be a potential therapeutic target for the treatment of NDDs.

Assessment for the Role of Serotonin Receptor Subtype 3 for the Analgesic Action of Morphine at the Spinal Level

2005 ◽  
Vol 18 (2) ◽  
pp. 113
Author(s):  
Myung Ha Yoon ◽  
Hong Buem Bae ◽  
Jeong Il Choi ◽  
Seok Jae Kim ◽  
Chang Mo Kim ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Receptor Subtype ◽  
Analgesic Action ◽  
Spinal Level ◽  
Subtype 3

Changes in serotonin levels and 5-HT receptor activity in duodenum of streptozotocin-diabetic rats

2001 ◽  
Vol 281 (3) ◽  
pp. G798-G808 ◽  
Author(s):  
H. Takahara ◽  
M. Fujimura ◽  
S. Taniguchi ◽  
N. Hayashi ◽  
T. Nakamura ◽  
...  
Keyword(s):  
Small Intestine ◽  
Motor Activity ◽  
Serotonin Receptor ◽  
Ex Vivo ◽  
Diabetic Rats ◽  
Receptor Activity ◽  
Diabetic Rat ◽  
Receptor Subtype ◽  
Serotonin Content ◽  
Rat Duodenum

Few previous studies have discussed the changes in serotonin receptor activity in the small intestine of diabetic animals. Therefore, we examined serotonin content in duodenal tissue and dose-dependent effects of serotonin agonists and antagonists on the motor activity of ex vivo vascularly perfused duodenum of streptozotocin (STZ)-diabetic rats. Serotonin content was significantly increased in enterochromaffin cells but not altered in serotonin-containing neurons in STZ-diabetic rats. Motor activity assessed by frequency, amplitude, and percent motility index per 10 min of pressure waves was reduced in the duodenum of diabetic rats, and this reduction was reversed by insulin treatment. Serotonin dose dependently increased the motor activity in control rat duodenum but only a higher concentration of serotonin increased the motor activity in diabetic rats. The 5-hydroxytryptamine (5-HT) receptor subtype 4 (5-HT4) antagonist SB-204070 dose dependently reduced motor activity in both control and diabetic rats, whereas the 5-HT3receptor antagonist azasetron, even at a higher concentration, failed to affect motor activity in diabetic rat duodenum but dose dependently reduced motor activity in control rat duodenum. These results suggest that 5-HT3receptor activity was impaired but 5-HT4receptor activity was intact in STZ-diabetic rat duodenum. Such an impairment of 5-HT3receptor activity may induce the motility disturbance in the small intestine of diabetes mellitus.

scholarly journals Role of some types of serotonin receptors in murine hypophyseal-testicular complex activation induced by the presence of a female

2003 ◽  
Vol 49 (6) ◽  
pp. 53-56
Author(s):  
T. G. Amstislavskaya ◽  
N. K. Popova
Keyword(s):  
Serotonin Receptors ◽  
Receptor Agonist ◽  
Serotonin Receptor ◽  
Receptive Female ◽  
Plasma Testosterone ◽  
Blood Levels ◽  
Inhibitory Effects ◽  
Sexual Activation ◽  
Different Types

Placement of a sexually receptive female mouse behind a partition that prevents physical contacts, but permits it to see and smell caused an increase in the blood levels of testosterone in male mice. The selective 5-HTIA-serotonin receptor agonist 08-OH- DPAT (0.1 mg/kg) and the mixed 5-HTIA/IB agonist eltoprazine, 3.0 and 10.0 mg/kg, blocked the activating effect of female exposure on the male pituitary-testicular system. The 5-HT/-receptor agonist p-MPPI (0.2 mg/kg) prevented the inhibitory effects of 8-OH-DPATand eltoprazine. The 5-HT/B-receptor agonist CGS- 12066A (1.0 and 2.0 mg/kg) exerted no effect while the mixed 5-HTIB/2C-receptor agonist TFMPP (5.2 mg/kg) inhibited a female-induced increase in the levels of male blood testosterone. The 5-HT/-receptor agonist keranserin (1.0 and 2.0 mg/kg) prevented a female-induced increase in the levels of testosterone. The 5-HT3-receptor agonist ondansetron (0.05 and 0.1 mg/kg) elevated the baseline level of plasma testosterone, but blocked receptive female-induced activation of the male hypothalamic-pituitary-testicular system (HPTS). It is concluded that 5-HTIA-receptors are involved in the control of male sexual activation. At the same time different types and even subtypes of the same type of 5-HT-receptors produce varying inhibitory and activating effects on the receptive female-induced activation of HPTS. Blocking of the female-induced activation of HPTS seems to be realized by involving 5-HTu- and 5-HT2C-receptors and its activation occurs with the participation of 5-HT^- and 5- HT3-receptors.

scholarly journals The Serotonin Receptor Subtype 5b Specifically Interacts with Serotonin Receptor Subtype 1A

2017 ◽  
Vol 10 ◽  
Author(s):  
Sabine Niebert ◽  
Gijsbert J. van Belle ◽  
Steffen Vogelgesang ◽  
Till Manzke ◽  
Marcus Niebert
Keyword(s):  
Serotonin Receptor ◽  
Receptor Subtype

scholarly journals Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5186 ◽  
Author(s):  
Serena Silvestro ◽  
Giovanni Schepici ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
G Protein ◽  
Serotonin Receptor ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Neurological Diseases ◽  
In Vivo Studies ◽  
Receptor Subtype ◽  
Transient Receptor Potential Vanilloid ◽  
Neuroprotective Effects ◽  
G Protein Coupled

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid known for its beneficial effects including antioxidant and anti-inflammatory properties. Moreover, CBD is a compound with antidepressant, anxiolytic, anticonvulsant and antipsychotic effects. Thanks to all these properties, the interest of the scientific community for it has grown. Indeed, CBD is a great candidate for the management of neurological diseases. The purpose of our review is to summarize the in vitro and in vivo studies published in the last 15 years that describe the biochemical and molecular mechanisms underlying the effects of CBD and its therapeutic application in neurological diseases. CBD exerts its neuroprotective effects through three G protein coupled-receptors (adenosine receptor subtype 2A, serotonin receptor subtype 1A and G protein-coupled receptor 55), one ligand-gated ion channel (transient receptor potential vanilloid channel-1) and one nuclear factor (peroxisome proliferator-activated receptor γ). Moreover, the therapeutical properties of CBD are also due to GABAergic modulation. In conclusion, CBD, through multi-target mechanisms, represents a valid therapeutic tool for the management of epilepsy, Alzheimer’s disease, multiple sclerosis and Parkinson’s disease.

scholarly journals The 1,3,5-Triazine Derivatives as Innovative Chemical Family of 5-HT6 Serotonin Receptor Agents with Therapeutic Perspectives for Cognitive Impairment

2019 ◽  
Vol 20 (14) ◽  
pp. 3420 ◽  
Author(s):  
Gniewomir Latacz ◽  
Annamaria Lubelska ◽  
Magdalena Jastrzębska-Więsek ◽  
Anna Partyka ◽  
Małgorzata Anna Marć ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Molecular Mechanisms ◽  
Binding Properties ◽  
Piperazine Derivatives ◽  
Behavioral Studies ◽  
Triazine Derivatives

Among serotonin receptors, the 5-HT6 subtype is the most controversial and the least known in the field of molecular mechanisms. The 5-HT6R ligands can be pivotal for innovative treatment of cognitive impairment, but none has reached pharmacological market, predominantly, due to insufficient “druglikeness” properties. Recently, 1,3,5-triazine-piperazine derivatives were identified as a new chemical family of potent 5-HT6R ligands. For the most active triazine 5-HT6R agents found (1–4), a wider binding profile and comprehensive in vitro evaluation of their drug-like parameters as well as behavioral studies and an influence on body mass in vivo were investigated within this work. Results indicated the most promising pharmacological/druglikeness profiles for 4-((1H-indol-3-yl)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (3) and 4-((2-isopropyl-5-methylphenoxy)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (4), which displayed a significant procognitive action and specific anxiolytic-like effects in the behavioral tests in vivo together with satisfied pharmaceutical and safety profiles in vitro. The thymol derivative (4) seems to be of higher importance as a new lead candidate, due to the innovative, non-indole and non-sulfone structure with the best 5-HT6R binding properties.

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