• Journal of Ginseng Research
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• v.25 no.2
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• pp.74-81
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• 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
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• v.11 no.2
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• pp.110-116
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• 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
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• v.50 no.12
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• pp.11.1-11.9
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• 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 Pain
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• v.18 no.2
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• pp.113-117
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• 2005

Background: Serotonin 3 receptor is involved in the modulation of nociceptive transmission in the spinal cord. The serotonin 3 receptor antagonist has been used for the management of opioid-induced nausea and vomiting. The aim of this study was to examine whether the analgesic effect of morphine is antagonized by serotonin 3 receptor antagonists at the spinal level. Methods: Rats were implanted with lumbar intrathecal catheters. For nociception, a formalin solution (5%, $50{\mu}l$) was injected into the hind paw of male Sprague-Dawley rats. To determine whether the effect of intrathecal morphine was mediated via serotonin 3 receptors, serotonin 3 receptor antagonists were intrathecally administered 10 min prior to the morphine delivery. Following the formalin injection, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. Results: Intrathecal morphine produced a dose-dependent suppression of the flinches in both phases during the formalin test. The analgesic action of morphine was not reversed by serotonin 3 receptor antagonists (LY-278,584, ondansetron), which had little per se effect on the formalin-induced nociception. Conclusions: Spinal serotonin 3 receptors may not be involved in the analgesia of morphine on a nociceptive state evoked by a formalin stimulus.

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

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

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

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.155-161
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• 1997

Serotonin has been implicated in the etiology of many disease states and may be particularly important mental illness, such as depression, anxiety, schizophrenia, sleep disorders, suicide, eating disorders, obsessive compulsive disorders, migraine and others. Many currently used treatments of these disorders are thought to act by modulating serotonergic function. The identification of many serotonin subtypes, most of which have been shown to have functional activity and differential distribution, has stimulated considerable effort into synthesizing selective ligands(drugs) to help understand their significance. This should understand the role of serotonin in mental disorders and these new drugs can be studied alone and in combination with other treatments in order to clarify the parameters of drug use for the clinical effect.

• YAKHAK HOEJI
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• v.35 no.4
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• pp.326-331
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• 1991

Brain serotonin and its utilization was investigated on stressed rats after feeding high tryptophan diet for a month. High tryptophan fed rats displayed significantly higher level of serum tryptophan, brain tryptophan, serotonin (5-hydroxytryptamine; 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) than the control diet fed rats. When rats were treated with 3 hour immobilization (IMMB) stress, serotonin turnover was slightly increased, but not statistically significant, in control diet group rats. However in high tryptophan diet rats, 3 hr IMMB stress resulted in statistically significantly (p<0.05) decreased the serum tryptophan, brain tryptophan and 5-HT level. The concentration of 5-HIAA was significantly increased indicating accelerated utilization of the brain 5-HT of the high trp. fed rat. The utilization pattern of the serotonin was found to be similar among young and adult rats. Rats on a tryptophan enriched diet displayed higher coping ability to the stress as they exhibited smaller increment of corticosterone level. A possble involvement of opioid system was suggested in serotonin utilization by measuring total $^{3}$[H]-naloxone binding in brain.

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