• Journal of Ginseng Research
• /
• v.25 no.2
• /
• pp.74-81
• /
• 2001

The effect of Korean Ginseng saponins (total saponin, PD saponin and PT saponin) on the serotonin type 3 receptor, which is known to be involved in nausea and vomiting following anticancer chemotherapy or the general anesthesia, was investigated. after in vitro transcribed recombinant serotonin type 3 receptor in the Xenopus laevis oocyte, classic two electrodes voltage clamp technique was used. All of ginseng saponins inhibited the response of the agonist, serotonin, on the serotonin type 3 receptor in a dose-dependent manner. PT saponin showed to have the inhibitory effect more than 2 times as potent as PD saponin. Total saponin shifted the serotonin dose response plot to the right (EC$\_$50/, 0.70$\pm$0.17 $\mu$M into 3.57$\pm$1.42 $\mu$M, and Hill coefficient, 2.14$\pm$0.60 into 1.52$\pm$1.00). Ginseng saponin did not change the reversal potential (∼0 mV) of serotonin type 3 receptor. These results suggest that Korean ginseng saponin may have the inhibitory effect on serotonin type 3 receptor.

• Korean Journal of Biological Psychiatry
• /
• v.11 no.2
• /
• pp.110-116
• /
• 2004

Objectives:Recently, polymorphisms of several serotonin genes have been suggested to be associated with suicide, but the results are still unclear. We examined whether the T102C polymorphisms of the serotonin 2A receptor gene and the G861C polymorphisms of the serotonin 1B receptor gene were associated with suicidal behavior using drug intoxication. Methods:The subjects were 52 patients who visited emergency room with suicidal behaviors. Fifty controls were selected from healthy volunteers matched for sex and age to the suicide subjects. The polymorphisms were analyzed with TaqMan$^{(R)}$ assay using primers based on previous studies. Results:The T102C polymorphism of the serotonin 2A receptor gene showed no significant difference between the suicidal attempters and controls in both genotype and allele frequency analyses(p=0.179 and p=0.422, respectively). There was no statistically significant difference between the suicidal attempters and the controls in the G861C polymorphism of the serotonin 1B receptor gene and any significant effect of the genotype distributions or the allele frequencies was not observed(p=0.092 and p=0.987, respectively). Conclusion:These findings suggest that the T102C polymorphism in serotonin 2A receptor gene and the G861C polymorphism in serotonin 1B receptor gene are not related to the susceptibility to suicide attempts using drugs. To clarify the genetic influences of the serotonergic system on suicidal behavior, the polymorphisms of other candidate genes in the serotonergic system should be studied with larger numbers of subjects.

• Experimental and Molecular Medicine
• /
• v.50 no.12
• /
• pp.11.1-11.9
• /
• 2018

Estrogen has diverse effects on cardiovascular function, including regulation of the contractile response to vasoactive substances such as serotonin. The serotonin system recently emerged as an important player in the regulation of vascular tone in humans. However, hyperreactivity to serotonin appears to be a critical factor for the pathophysiology of hypertension. In this study, we examined the modulatory mechanisms of estrogen in serotonin-induced vasoconstriction by using a combinatory approach of isometric tension measurements, molecular biology, and patch-clamp techniques. $17{\beta}$-Estradiol (E2) elicited a significant and concentration-dependent relaxation of serotonin-induced contraction in deendothelialized aortic strips isolated from male rats. E2 triggered a relaxation of serotonin-induced contraction even in the presence of tamoxifen, an estrogen receptor antagonist, suggesting that E2-induced changes are not mediated by estrogen receptor. Patch-clamp studies in rat arterial myocytes showed that E2 prevented Kv channel inhibition induced by serotonin. Serotonin increased Src activation in arterial smooth muscle required for contraction, which was significantly inhibited by E2. The estrogen receptor-independent inhibition of Src by E2 was confirmed in HEK293T cells that do not express estrogen receptor. Taken together, these results suggest that estrogen exerts vasodilatory effects on serotonin-precontracted arteries via Src, implying a critical role for estrogen in the prevention of vascular hyperreactivity to serotonin.

• The Korean Journal of Physiology
• /
• v.24 no.1
• /
• pp.67-76
• /
• 1990

The contractile mechanisms of serotonin were investigated in the renal artery of a rabbit. The helical strips of isolated renal artery were immersed in the normal or $Ca^{2+}$-free tris-buffered Tyrode's solution, which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$. The contraction by serotonin or norepinephrine (NE) began at $1{\times}10^{-7}\;M$ and reached the maximal contraction at $1{\times}10^{-5}\;M$. The maximal contraction by serotonin corresponded to $58.1{\pm}4.2%$ of maximal contraction by NE. Cyproheptadine, a serotonin receptor blocker, shifted the concentration-response curve to the right without any reduction in the maximum response but shifted that of NE to the right with reduction in maximum response. And phentolamine, an ${\alpha}-receptor$ blocker, shifted the concentration-response curve of serotonin or NE without any reduction in maximum responses. The $pA_{2}$ values for cyproheptadine against serotonin and NE were $10.35{\pm}0.04$ and $8.45{\pm}0.13$, respectively. The $pA_{2}$ values for phentolamine against serotonin and NE were $6.87{\pm}0.04$ and $8.14{\pm}0.08$, respectively. after the pretreatment with 6-hydroxydopamine, the contraction induced by 100 mM $K^{+}$, tyramine and serotonin reduced to $83.0{\pm}2.0$, $26.8{\pm}6.2$ and $82.0{\pm}3.5%$ of control, respectively. The contraction by serotonin in the $Ca^{2+}$-free Tyrode's solution was increased and sustained with the addition of $Ca^{2+}$ extracellulary. The serotonin-sensitive intracellular $Ca^{2+}$ pool was depleted completely by the pretreatment with NE, but the NE-sensitive intracellular $Ca^{2+}$ pool was depleted partially by the pretreatment with serotonin. From the above results, it is suggested that the contraction induced by serotonin in the renal artery of a rabbit may be due to mechanisms in which serotonin acts directly on specific serotonin receptors and also acts indirectly on ${\alpha}-adrenoceptors$ by displacing NE from neuronal stores.

• Biomolecules & Therapeutics
• /
• v.25 no.5
• /
• pp.497-503
• /
• 2017

Recent reports claimed that glucosylsphingosine (GS) is highly accumulated and specifically evoking itch-scratch responses in the skins of atopic dermatitis (AD) patients. However, it was unclear how GS can trigger itch-scratch responses, since there were no known molecular singling pathways revealed yet. In the present study, it was verified for the first time that GS can activate mouse serotonin receptor 2a (mHtr2a) and 2b (mHtr2b), but not 2c (mHtr2c) that are expressed in HEK293T cells. Specifically, effects of GS on all mouse serotonin receptor 2 subfamily were evaluated by calcium imaging techniques. The GS-induced intracellular calcium increase was dose-dependent, and antagonists such as ketanserin (Htr2a antagonist) and RS-127445 (Htr2b antagonist) significantly blocked the GS-induced responses. Moreover, the proposed GS-induced responses appear to be mediated by phospholipase C (PLC), since pretreatment of a PLC inhibitor U-73122 abolished the GS-induced responses. Additionally, the GS-induced calcium influx is probably mediated by endogenous TRPC ion channels in HEK293T cells, since pretreatment of SKF-96365, an inhibitor for TRPC, significantly suppressed GS-induced response. In conclusion, the present study revealed for the first time that GS can stimulate mHtr2a and mHtr2b to induce calcium influx, by utilizing PLC-dependent pathway afterwards. Considering that GS is regarded as a pruritogen in AD, the present study implicates a novel GS-induced itch signaling pathway.

• BMB Reports
• /
• v.38 no.2
• /
• pp.238-242
• /
• 2005

5-HT2A is one of major serotonin receptor that is involved in the action of serotonin-targeting drugs. Previous clinical studies have shown an unexpected association between lower cholesterol level and psychiatric diseases, in which T102C polymorphism of HTR2A, gene of 5-HT2A serotonin receptor, might be involved. Therefore, we hypothesized a potential association between lower cholesterol level and T102C polymorphism. The effect of the T102C polymorphism on the serum lipid profiles of 646 subjects without specific psychiatric disease was investigated. Genotype was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. There were significantly lower levels of total cholesterol ($193.6{\pm}35.0$ versus $202.1{\pm}45.5\;mg/dl$, p = 0.016) and HDL-cholesterol ($42.7{\pm}11.6$ versus $46.3{\pm}12.7\;mg/dl$, p = 0.004) in CC genotype than non-CC genotypes. Moreover, multivariate analysis showed that the CC genotype is a strong predictor of a lower HDL-cholesterol level (p < 0.001). In conclusion, this study shows that the CC genotype of the HTR2A gene is related to lower HDL-cholesterol level in Koreans. This is the first demonstration showing the potential genetic relationship between the serotonin receptor gene polymorphism and the HDL-cholesterol level.

• Biomolecules & Therapeutics
• /
• v.16 no.4
• /
• pp.299-305
• /
• 2008

Active cardiovascular anaphylactic response was induced in ovalbumin-sensitized, pithed Sprague-Dawley and Wistar rats. On intravenous administration of the antigen, ovalbumin, marked tachycardia and pressor responses were immediately elicited. Thereafter, a delayed long-lasting severe hypotensive response was observed. These anaphylactic cardiovascular responses were maximal 2-3 weeks after the sensitization, and the response was slightly diminished 6 weeks after sensitization. The immediate pressor response was blocked by a non-selective serotonin antagonist methysergide at a dose-dependent manner, but not by histamine receptor antagonists mepyramine (pyrilamine) or cimetidine. The delayed hypotension was reduced either by histamine $H_1$ receptor antagonist mepyramine or $H_2$ receptor antagonist cimetidine, both in a dose-dependent manner. The tachycardic response was not influenced by serotonin or histamine receptor antagonists examined in this study. Differently from the cardiovascular responses, there was no observable bronchial contraction in Sprague-Dawley rat trachea in contrast to Wistar rat where the trachea contracted to in vitro antigen challenge. The cardiovascular anaphylactic model seems to be useful for studying cardiovascular events that occur exclusively in peripheral heart-blood vessel systems. The involvement of two major anaphylactic mediators, serotonin and histamine, is partially demonstrated.

• Journal of Integrative Natural Science
• /
• v.9 no.2
• /
• pp.128-135
• /
• 2016

5-hydroxytryptamine (serotonin) receptor ($5-HT_7R$) 7 is one of G-Protein coupled receptors, which is activated by the neurotransmitter Serotonin. After activation by serotonin, $5-HT_7$ activates the production of the intracellular signaling molecule cyclic AMP. $5-HT_7$ receptor has been found to be involved in the pathophysiology of various disorders. It is reported that $5-HT_7$ receptor antagonists can be used as antidepressant agents. In this study, we report the important structural and chemical parameters for 2-methoxyphenylpiperazinylakanamides as $5-HT_7R$ inhibitors. A 3D QSAR study based on comparative molecular field analysis (CoMFA) was performed. The best predictions were obtained for the best CoMFA model with $q^2$ of 0.594 with 6 components, $r^2$ of 0.986, Fisher value as 60.607, and an estimated standard error of 0.043. The predictive ability of the test set was 0.602. Results obtained the CoMFA models suggest that the data are well fitted and have high predictive ability. The contour maps are generated and studied. The contour analyses may serve as tool in the future for designing of novel and more potent $5-HT_7R$ derivatives.

• BMB Reports
• /
• v.56 no.10
• /
• pp.527-536
• /
• 2023

Serotonin receptors, also known as 5-HT receptors, belong to the G protein-coupled receptors (GPCRs) superfamily. They mediate the effects of serotonin, a neurotransmitter that plays a key role in a wide range of functions including mood regulation, cognition and appetite. The functions of serotonin are mediated by a family of 5-HT receptors including 12 GPCRs belonging to six major families: 5-HT₁, 5-HT₂, 5-HT₄, 5-HT₅, 5-HT₆ and 5-HT₇. Despite their distinct characteristics and functions, these receptors' subtypes share common structural features and signaling mechanisms. Understanding the structure, functions and pharmacology of the serotonin receptor family is essential for unraveling the complexities of serotonin signaling and developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specific receptor subtypes is challenging due to the structural similarities in their orthosteric binding sites. This review focuses on the recent advancements in the structural studies of 5-HT receptors, highlighting the key structural features of each subtype and shedding light on their potential as targets for mental health and neurological disorders (such as depression, anxiety, schizophrenia, and migraine) drugs.

• Genomics & Informatics
• /
• v.5 no.2
• /
• pp.77-82
• /
• 2007

Serotonin (5-HT), the endogenous nonselective 5-HT receptor agonist, activates the inositol-1,4,5-triphosphate/calcium $(InsP3/Ca^{2+})$ signaling pathway and exerts both stimulatory and inhibitory actions on cAMP production and neuromodulin secretion in rat hypothalamic neurons. Specific mRNA transcripts for 5-HT1A, 5-HT2C and 5-HT4 were identified in rat hypothalamic neurons. These experiments were supported by combined techniques such as cAMP and a $Ca^{2+}$ assays in order to elucidate the associated receptors and signaling pathways. The cAMP production and neuromodulin release were profoundly inhibited during the activation of the Gi-coupled 5-HT1A receptor. Treatment with a selective agonist to activate the Gq-coupled 5-HT2C receptor stimulated InsP3 production and caused $Ca^{2+}$ release from the sarcoplasmic reticulum. Selective activation of the Gs-coupled 5-HT4 receptor also stimulated cAMP production, and caused an increase in neuromodulin secretion. These findings demonstrate the ability of 5-HT receptor subtypes expressed in neurons to induce neuromodulin production. This leads to the activation of single or multiple G-proteins which regulate the $InsP3/Ca^{2+}/PLC-{\gamma}$ and adenyl cyclase / cAMP signaling pathways.