Serotonin에 의한 가토 신동맥 평활근 수축기전

이우영,김세훈,장석종,Lee, Woo-Young,Kim, Se-Hoon,Chang, Seok-Jong 대한생리학회 1990 대한생리학회지 Vol.24 No.1

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.

Expression of the serotonin 1A receptor in the horse brain

최연주,윤민중 사단법인 한국동물생명공학회 2023 Journal of Animal Reproduction and Biotechnology Vol.38 No.2

Background: Serotonin receptors can be divided into seven different families with various subtypes. The serotonin 1A (5-HT1A) receptor is one of the most abundant subtypes in animal brains. The expression of 5-HT1A receptors in the brain has been reported in various animals but has not been studied in horses. The 5-HT1A receptor functions related to emotions and behaviors, thus it is important to understand the functional effects and distribution of 5-HT1A receptors in horses to better understand horse behavior and its associated mechanism. Methods: Brain samples from seven different regions, which were the frontal, central, and posterior cerebral cortices, cerebellar cortex and medulla, thalamus, and hypothalamus, were collected from six horses. Western blot analysis was performed to validate the cross-reactivity of rabbit anti-5-HT1A receptor antibody in horse samples. Immunofluorescence was performed to evaluate the localization of 5-HT1A receptors in the brains. Results: The protein bands of 5-HT1A receptor appeared at approximately 50 kDa in the frontal, central, and posterior cerebral cortices, cerebellar cortex, thalamus, and hypothalamus. In contrast, no band was observed in the cerebellar medulla. Immunofluorescence analysis showed that the cytoplasm of neurons in the cerebral cortices, thalamus, and hypothalamus were immunostained for 5-HT1A receptors. In the cerebellar cortex, 5-HT1A was localized in the cytoplasm of Purkinje cells. Conclusions: In conclusion, the study suggests that 5-HT and 5-HT1A receptor systems may play important roles in the central nervous system of horses, based on the widespread distribution of the receptors in the horse brain.

Expression of the serotonin 1A receptor in the horse brain

Yeonju Choi,Minjung Yoon The Korean Society of Animal Reproduction and Biot 2023 한국동물생명공학회지 Vol.38 No.2

Background: Serotonin receptors can be divided into seven different families with various subtypes. The serotonin 1A (5-HT1A) receptor is one of the most abundant subtypes in animal brains. The expression of 5-HT1A receptors in the brain has been reported in various animals but has not been studied in horses. The 5-HT1A receptor functions related to emotions and behaviors, thus it is important to understand the functional effects and distribution of 5-HT1A receptors in horses to better understand horse behavior and its associated mechanism. Methods: Brain samples from seven different regions, which were the frontal, central, and posterior cerebral cortices, cerebellar cortex and medulla, thalamus, and hypothalamus, were collected from six horses. Western blot analysis was performed to validate the cross-reactivity of rabbit anti-5-HT1A receptor antibody in horse samples. Immunofluorescence was performed to evaluate the localization of 5-HT1A receptors in the brains. Results: The protein bands of 5-HT1A receptor appeared at approximately 50 kDa in the frontal, central, and posterior cerebral cortices, cerebellar cortex, thalamus, and hypothalamus. In contrast, no band was observed in the cerebellar medulla. Immunofluorescence analysis showed that the cytoplasm of neurons in the cerebral cortices, thalamus, and hypothalamus were immunostained for 5-HT1A receptors. In the cerebellar cortex, 5-HT1A was localized in the cytoplasm of Purkinje cells. Conclusions: In conclusion, the study suggests that 5-HT and 5-HT1A receptor systems may play important roles in the central nervous system of horses, based on the widespread distribution of the receptors in the horse brain.

흰쥐 선조체 및 흑질의 Serotonin 수용체에 대한 ^3H-ketanserin을 이용한 전자현미경 자기방사법적 연구

이희래,이혜성,배영숙 이화여자대학교 생명과학연구소 1990 생명과학연구논문집 Vol.1 No.-

흰 쥐의 측뇌실에 ^3H-ketanserin을 주입한 다음 신줄무늬체 및 흑색질에서 serotonin 수용체의 분포양상을 전자현미경 자기방사법으로 관찰하여 다음과 같은 결과를 얻었다. 신줄무늬체에서 은입자는 대부분이 가지돌기 및 축삭가지와 연접에 표지되었다. 표지된 연접에서 축삭종말은 소원형 및 다형소포를 함유하였고 비대칭의 축삭가지돌기연접을 형성하였다. 흑색질에서 표지양상은 신줄무늬체와 거의 같았다. 이러한 결과에 따라서 신줄무늬체 및 흑색질에서 serotonin-2 수용체는 주로 소원형 및 다형소포를 함유한 비대칭의 축삭가지돌기연접에 분포하며 이 수용체의 분포는 serotonin신경섬유의 분포와 밀접한 관련이 있는 것으로 생각된다. It has been demonstrated that some serotoninergic axonal branches from the dorsal rap heneurons prject to the neostriatum and the substantia nigra, and also has been reported that serotonin receptors distribute in the same regions of the mammalian brain. It is interesting to analyse how the distribution of serotonin receptors correlates with that of serotoninergic nerve terminals in the brain. This study was performed to identify the serotoninergic nerve terminals in the neostriatum and the substantis nigra of the rat. Identification of the serotoninergic nerve terminals at ultrastructural level has been done by autoradiography after cerebroventricular administration of ³H-ketanserin as a ligand. In the neruropil of the neostriatum, most of silver grains were labeled on the thin branches of axons and dendrites and some of them on soma or myelinated axons. In the cases of labeled synapes, axon terminals contained round and pleomorphic vesicles and showed asymmetric contact with dendrites or dendritic spines. In the substantia nigra, the distribution patterns of labeled siver grains beared a close paralell to neostriatum. But in the labeled synapes from this region, axon terminals ocntaining small round vesicles made mainly asymmetric synapses with dendrites. The observations made in this study indicate that serotonin-2 receptors are present in the asymmetric axo-dendritic synapses with small round and pleomorphic vesicles and the distribution of the serotonin-2 receptors have closely with that of serotoninergic fibers in the neostriatum and the substantia nigra of rat.

Selective serotonin reuptake inhibitor escitalopram inhibits 5-HT₃ receptor currents in NCB-20 cells

Park, Yong Soo,Sung, Ki-Wug The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.6

Escitalopram is one of selective serotonin reuptake inhibitor antidepressants. As an S-enantiomer of citalopram, it shows better therapeutic outcome in depression and anxiety disorder treatment because it has higher selectivity for serotonin reuptake transporter than citalopram. The objective of this study was to determine the direct inhibitory effect of escitalopram on 5-hydroxytryptamine type 3 ($5-HT_3$) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through $5-HT_3$ receptors. Using a wholecell voltage clamp method, we recorded currents of $5-HT_3$ receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. $EC_{50}$ of 5-HT on $5-HT_3$ receptor currents was increased by escitalopram while the maximal peak amplitude was reduced by escitalopram. The inhibitory effect of escitalopram was voltage independent. Escitalopram worked more effectively when it was co-applied with 5-HT than pre-application of escitalopram. Moreover, escitalopram showed fast association and dissociation to the open state of $5-HT_3$ receptor channel with accelerating receptor desensitization. Although escitalopram accelerated $5-HT_3$ receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit $5-HT_3$ receptor currents in a non-competitive manner with the mechanism of open channel blocking.

Selective serotonin reuptake inhibitor escitalopram inhibits 5-HT3 receptor currents in NCB-20 cells

Yong Soo Park,Ki-Wug Sung 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.6

Escitalopram is one of selective serotonin reuptake inhibitor antidepressants. As an S-enantiomer of citalopram, it shows better therapeutic outcome in depression and anxiety disorder treatment because it has higher selectivity for serotonin reuptake transporter than citalopram. The objective of this study was to determine the direct inhibitory effect of escitalopram on 5-hydroxytryptamine type 3 (5-HT3) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through 5-HT3 receptors. Using a wholecell voltage clamp method, we recorded currents of 5-HT3 receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express 5-HT3 receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. EC50 of 5-HT on 5-HT3 receptor currents was increased by escitalopram while the maximal peak amplitude was reduced by escitalopram. The inhibitory effect of escitalopram was voltage independent. Escitalopram worked more effectively when it was co-applied with 5-HT than pre-application of escitalopram. Moreover, escitalopram showed fast association and dissociation to the open state of 5-HT3 receptor channel with accelerating receptor desensitization. Although escitalopram accelerated 5-HT3 receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit 5-HT3 receptor currents in a non-competitive manner with the mechanism of open channel blocking.

Selective serotonin reuptake inhibitor escitalopram inhibits 5-HT3 receptor currents in NCB-20 cells

박용수,성기욱 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.6

Escitalopram is one of selective serotonin reuptake inhibitor antidepressants. As an S-enantiomer of citalopram, it shows better therapeutic outcome in depression and anxiety disorder treatment because it has higher selectivity for serotonin reuptake transporter than citalopram. The objective of this study was to determine the direct inhibitory effect of escitalopram on 5-hydroxytryptamine type 3 (5-HT3) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through 5-HT3 receptors. Using a wholecell voltage clamp method, we recorded currents of 5-HT3 receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express 5-HT3 receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. EC50 of 5-HT on 5-HT3 receptor currents was increased by escitalopram while the maximal peak amplitude was reduced by escitalopram. The inhibitory effect of escitalopram was voltage independent. Escitalopram worked more effectively when it was co-applied with 5-HT than pre-application of escitalopram. Moreover, escitalopram showed fast association and dissociation to the open state of 5-HT3 receptor channel with accelerating receptor desensitization. Although escitalopram accelerated 5-HT3 receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit 5-HT3 receptor currents in a non-competitive manner with the mechanism of open channel blocking

The Role of Serotonin in Ventricular Repolarization in Pregnant Mice

Shanyu Cui,박혜원,박혜림,문다솜,이승현,김효은,윤누리,김하일,Michael Kim,박희남,이문형,정보영 연세대학교의과대학 2018 Yonsei medical journal Vol.59 No.2

Purpose: The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternalserotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. Materials and Methods: We measured current amplitudes and the expression levels of voltage-gated K+ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygousknockout mice (Htr3a-/--NP). Results: During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT intervalin WT-NP mice, but not in WT-LP and Htr3a-/--NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increasedthe trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Conclusion: Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents.

Resveratrol Enhances 5-Hydroxytryptamine Type 3A Receptor-Mediated Ion Currents: The Role of Arginine 222 Residue in Pre-transmembrane Domain I

Lee, Byung-Hwan,Hwang, Sung-Hee,Choi, Sun-Hye,Shin, Tae-Joon,Kang, Jiyeon,Lee, Sang-Mok,Nah, Seung-Yeol Pharmaceutical Society of Japan 2011 Biological & pharmaceutical bulletin Vol.34 No.4

<P>Resveratrol, which is found in grapes, red wine, and berries, has many beneficial health effects, such as anti-cancer, neuro-protective, anti-inflammatory, and life-prolonging effects. However, the cellular mechanisms by which resveratrol acts are relatively unknown, especially in terms of possible regulation of receptors involved in synaptic transmission. 5-Hydroxytryptamine type 3A (5-HT<SUB>3A</SUB>) receptor is one of several ligand-gated ion channels involved in fast synaptic transmission. In the present study, we investigated the effect of resveratrol on mouse 5-HT<SUB>3A</SUB> receptor channel activity. 5-HT<SUB>3A</SUB> receptor was expressed in <I>Xenopus</I> oocytes, and the current was measured using a two-electrode voltage clamp technique. Treatment of resveratrol itself had no effect on the oocytes injected with H<SUB>2</SUB>O as well as on the oocytes injected with 5-HT<SUB>3A</SUB> receptor cRNA. In the oocytes injected with 5-HT<SUB>3A</SUB> receptor cRNA, co- or pre-treatment of resveratrol with 5-HT potentiated 5-HT-induced inward peak current (<I>I</I><SUB>5-HT</SUB>) with concentration-, reversible, and voltage-independent manners. The EC<SUB>50</SUB> of resveratrol was 28.0±2.4 μ<SMALL>M</SMALL>. The presence of resveratrol caused a leftward shift of 5-HT concentration–response curve. Protein kinase C (PKC) activator or inhibitor had no effect on resveratrol action on <I>I</I><SUB>5-HT</SUB>. Site-directed mutations of pre-transmembrane domain 1 (pre-TM1) such as R222A, R222D, R222E, R222K, and R222T abolished or attenuated resveratrol-induced enhancement of <I>I</I><SUB>5-HT</SUB>, indicating that resveratrol might interact with pre-TM1 of 5-HT<SUB>3A</SUB> receptor. These results indicate that resveratrol might regulate 5-HT<SUB>3A</SUB> receptor channel activity <I>via</I> interaction with the N-terminal domain and these results further show that resveratrol-mediated regulation of 5-HT<SUB>3A</SUB> receptor channel activity might be one of cellular mechanisms of resveratrol action.</P>

Desflurane의 세로토닌3A형 수용체 항진작용에 대한 인삼사포닌의 효과

최승호 ( Seung Ho Choi ),김미경 ( Mi Kyeong Kim ),구본녀 ( Bon Nyeo Koo ),민경태 ( Kyeong Tae Min ) 대한마취과학회 2009 Korean Journal of Anesthesiology Vol.56 No.6

Background: Postoperative nausea and vomiting (PONV) is the most frequent and discomforting side effect following general anesthesia. Most volatile anesthetics have a potent effect on serotonin (5-hydroxydtryptamine, 5-HT) type 3 receptor mediating PONV, and their antagonists have been currently used effectively to prevent and/or reduce the incidence and severity of PONV. The authors reported previously that ginsenosides have inhibitory effect on 5-HT(3A) receptor. In this study we intended to elucidate the inhibitory effect of ginsenosides on the potentiated 5-HT(3A) receptor by desflurane. Methods: After in vitro transcription of the recombinant mouse 5-HT(3A) receptor in the Xenopus laevis oocyte, we examined the effects of ginsenosides (g-Rb1, g-Rg1, g-Rd, g-Rg2) as well as ginsenoside metabolite, compound K on the modulation of desflurane by measuring currents flowing through 5-HT(3A) receptor using two-electrode voltage clamp technique. Results: Although normalized inhibitory responses of ginsenosides were same regardless of desflurane, some ginsenosides such as g-Rd, g-Rg2, and g-Rg1 showed potential inhibition to the enhanced 5-HT induced current of 5-HT(3A) receptor by desflurane. Conclusions: Although ginsenosides have substantial inhibitory effect on 5-HT(3A) receptor, the effects of ginsenoside on potentiation by desflurane of 5-HT induced current via recombinant 5HT(3A) receptor may depend on the types of ginsenoside, which suggesting that ginsenoside might have an antagonistic action to nausea and vomiting associated with volatile anesthetics. (Korean J Anesthesiol 2009; 56: 681~6)