• Toxicological Research
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• 제6권1호
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• pp.75-88
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• 1990

The characteristics of dopamine uptake, D-1 and D-2 receptors after acute and subacute cocaine administration were determind in striatum from WKY and SHR. Cocaine was administered either acutely (40 mg/kg, s.c.) or twice daily (20 mg/kg, s.c.) for 3 and 7 days in 9-wk old WKY and SHR. Rats were sacrificed 30 min, 2 or 24 h after the single injection and 18 h after the last administration to the subacutely treated group. The changes in dopamine uptake, dopamine uptake sites, D-1 and D-2 receptors were determined using $(^3H)$dopamine, $(^3H)$-GBR-12935, $(^3H)$SCH-23390 and $(^3H)$sulpiride, respectively. In acutely treated rats, significant increases in $V_{max}$of dopamine uptake were observed 30 min after the cocanine injection in both strains without changes in $K_m$ values. The in vitro $IC_{50}$for cocaine was significantly decreased 30 min in WKY and 2 h in SHR. However, that for in vitro GBR-12909 was significantly increased 30 min and 2 h in both strains. Also densities of $(^3H)$-GBR-12935 binding sites were significantly increased 30 min and 2 h without changes in their $K_d$. Significant increases in D-2 receptor density were observed 30 min, 2 or 24 h after acute injection in both strains without changes in their affinities. The density of D-1 receptor was significantly decreased 30 min after the injection in WKY, but not in SHR. In subacutely treated rats, a significant increase in $K_m$ of dopamine uptake was observed in 7-day treated SHR. The in vitro $IC_{50}$fot GBR-12909 was significantly increased in 3-day treated WKY. The density of D-1 receptors was significantly increased in 3- and 7-day treated WKY, but not in SHR. The affinity of both binding sites remained unchanged. The results suggest that cocanine administration alters dopamine uptake, characteristics of dopamine uptake sites and dopamine receptor binding characteristics in rat brain. Furthermore, D-1 and D-2 dopamine receptors appear to be differently regulated.

• The Korean Journal of Physiology and Pharmacology
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• 제12권1호
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• pp.13-23
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• 2008

The aim of the present study was designed to establish comparatively the inhibitory effects of $D_1$-like and $D_2$-like dopaminergic receptor agonists, SKF81297 and R(-)-TNPA on the release of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. SKF81297 $(30{\mu}M)$ and R-(-)-TNPA $(30{\mu}M)$ perfused into an adrenal vein for 60 min, produced great inhibition in the CA secretory responses evoked by ACh $(5.32{\times}10^{-3}\;M)$, DMPP $(10^{-4}\;M)$, McN-A-343 $(10^{-4}\;M)$, high $K^+$ $(5.6{\times}10^{-2}\;M)$, Bay-K-8644 $(10{\mu}M)$, and cyclopiazonic acid $(10{\mu}M)$, respectively. For the release of CA evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: SKF81297>R-(-)-TNPA. However, R(+)-SCH23390, a selectve $D_1$-like dopaminergic receptor antagonist, and S(-)-raclopride, a selectve $D_2$-like dopaminergic receptor antagonist, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid only for $0{\sim}4$ min. The rank order for the enhancement of CA release evoked by high $K^+$, McN-A-343 and cyclopiazonic acid was R(+)-SCH23390>S(-)-raclopride. Also, the rank order for ACh, DMPP and Bay-K-8644 was S(-)-raclopride > R(+)-SCH23390. Taken together, these results demonstrate that both SKF81297 and R-(-)-TNPA inhibit the CA release evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland without affecting the basal release, respectively, but both R(+)-SCH23390 and S(-)-raclopride facilitate the CA release evoked by them. It seems likely that the inhibitory effects of SKF81297 and R-(-)-TNPA are mediated by the activation of $D_1$-like and $D_2$-like dopaminergic receptors located on the rat adrenomedullary chromaffin cells, respectively, whereas the facilitatory effects of R(+)-SCH23390 and S(-)-raclopride are mediated by the blockade of $D_1$-like and $D_2$-like dopaminergic receptors, respectively: this action is possibly associated with extra- and intracellular calcium mobilization. Based on these results, it is thought that the presence of dopaminergic $D_1$ receptors may play an important role in regulation of the rat adrenomedullary CA secretion, in addition to well-known dopaminergic $D_2$ receptors.

• Journal of Gastric Cancer
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• 제6권3호
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• pp.132-138
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• 2006

목적: 도파민은 중추신경전달물질이지만 위장관에서 도파민수용체와 결합하여 점막상피세포 증식, 상피세포의 보호, 위암 세포증식과 관련이 있는 것으로 알려져 있다. 본 연구에서는 위암에서 기원한 세포주를 이용하여 도파민과 각각의 도파민 수용체가 위암 세포 증식과 억제에 작용하는 역할에 대해 알아보았다. 대상 및 방법: 위암세포기원에서 각각 유래한 세포주인 SNU601과 KCU-C2를 이용하여 RNA 추출 후 RT-PCR 시행 후 도파민수용체 D1, D2L과 D2S 각각에 대한 primer로 PCR을 시행하여 수용체 유전자의 상대적인 발현정도를 측정하였다. 도파민과 Dl 수용체의 대항제인 SCH 23390과 D2 수용체 대항제인 raclopride를 사용하여 약물처리에 따른 위암세포주에서 세포 증식에 대한 분석을 하였다. 결과: KCU-C2 세포주에서 D1과 D2L과 D2S 유전자 mRNA의 상대적인 발현정도는 모두 높은 발현을 보였지만, SNU 601 세포주에는 mRNA의 발현이 모두 낮은 수준이었으며, 특히 D2L mRNA는 발현되고 있지 않았다. 약물처리에 따른 위암세포주에서 세포증식에 대한 분석에서는 D1과 D2S 수용체를 통한 도파민의 신호는 세포의 증식을 억제하였고 D2L 수용체를 통한 도파민의 신호는 세포의 증식을 유도하였다. 결론: 본 연구를 통해 도파민이 위암의 세포증식과 억제에 관여하며, 도파민의 이러한 효과는 도파민의 신호가 어느 수용체를 통해 전달되었느냐에 따라 위암세포의 증식과 억제가 이루어짐을 알 수 있었다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.270.2-270.2
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• 2002

Dopamine D2 and D3 receptors (D2R and D3R) belong to pharmacological D2R family and share similar structural and functional characteristics. Elucidation of their differential functional characteristics is important for understanding their roles in brain. ERK1/2 was chosen as an example of signaling component of D2R and D3R and systemic studies were conducted to understand the regulatory mechanisms on ERK1/2 activation. (omitted)

• Nutrition Research and Practice
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• 제16권1호
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• pp.1-13
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• 2022

BACKGROUND/OBJECTIVES: Bitter taste receptors are taste signaling pathway mediators, and are also expressed and function in extra-gustatory organs. Skin aging affects the quality of life and may lead to medical issues. The purpose of this study was to better understand the anti-skin aging effects of bitter taste receptors in D-galactose (D-gal)-induced aged human keratinocytes, HaCaT cells. MATERIALS/METHODS: Expressions of bitter taste receptors in HaCaT cells and mouse skin tissues were examined by polymerase chain reaction assay. Bitter taste receptor was overexpressed in HaCaT cells, and D-gal was treated to induce aging. We examined the effects of bitter taste receptors on aging by using β-galactosidase assay, wound healing assay, and Western blot assay. RESULTS: TAS2R16 and TAS2R10 were expressed in HaCaT cells and were upregulated by D-gal treatment. TAS2R16 exerted protective effects against skin aging by regulating p53 and p21, antioxidant enzymes, the SIRT1/mechanistic target of rapamycin pathway, cell migration, and epithelial-mesenchymal transition markers. TAS2R10 was further examined to confirm a role of TAS2R16 in cellular senescence and wound healing in D-gal-induced aged HaCaT cells. CONCLUSIONS: Our results suggest a novel potential preventive role of these receptors on skin aging by regulating cellular senescence and wound healing in human keratinocyte, HaCaT.

• 대한핵의학회지
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• 제31권4호
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• pp.421-426
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• 1997

[$^{18}F$]FMBS는 도파민 $D_2$ 수용체 방사성추적자로서 유망한 성질을 지니고 있다. [$^{18}F$]FMBS는 비교적 높은 특이결합/비특이결합 비를 제공하며, 그 체내결합은 도파민 $D_2$ 수용체에 대하여 높은 특이성과 선택성을 보인다. 도파빈 $D_2$ 수용체 측정을 위한 보다 적합한 PET 방사성추적자를 얻기 위해서는 [$^{18}F$]FMBS의 낮은 뇌섭취와 느린 역학을 개선할 수 있는 화학적 구조의 변형이 시도되어야 하며, [$^{18}F$]FMBS는 이러한 시도의 골격이 될 수 있을 것으로 믿는다.

• Archives of Pharmacal Research
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• 제17권6호
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• pp.398-404
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• 1994

The behavioral response, depamine metabolism, and characteristics of dopamine subtypes after developing the hyperlycemia were studied in the striata of rats. In animals developed hyperglycemia, the on-set duration of cataleptic behavior responded to SCH 23390 injection was delayed abd shortened, respectively. However, the cataleptic response to spiperone occurred significantly earlier in on-set and prolonged in duration. Dopamine metabolites, dihydroxyphenylacetic acid (DDPAC) and homovanillic acid (HVA), were significantly reduced in teh striata of hyeprglycemic rats. However, level of DA was significantly increased. It is noted that the ratios of DOPAC and HVA to DA were decreased, suggesting decreased tumover of DA. The affinity of striatal D-1 receptors was significantly increased without changes in the number of binding sites, while the maximum binding number of D-2 recptors was significantly increased without affecting its affinity in the diabetic rats. These results indicate that the dopaminergic activity in striatia was altered in hyperglycemic rats. Furthermore, it suggests that the upregulation of dopamine receptors might be due to the decreased dopamine matabolism.

• BMB Reports
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• 제28권3호
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• pp.221-226
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• 1995

Dopamine mediates inhibitory responses in Helix aspersa neurons from the right parietal lobe ("F-lobe") of the circumoesophageal ganglia. The effects appeared as a dose-dependent hyperpolarization of the plasma membrane and a decrease in the occurrence of spontaneous action potentials. The average hyperpolarization with 5 ${\mu}m$ dopamine was -12 mV (${\pm}1.5$mV, S.D., n=12). Dopamine also modulated the currents 'responsible for shaping the action potentials in these neurons. When dopamine was added and action potentials were triggered by an injection of current, the initial depolarization was slowed, the amplitude and the duration of action potentials were decreased, and the after-hyperpolarization was more pronounced. The amplitude and the duration of action potential were reduced about 15 mV and about 13% by 5 ${\mu}m$ dopamine, respectively. The effects of dopamine on the resting membrane potentials and the action potentials of Helix neurons were dose-dependent in the concentration range 0.1 ${\mu}m$ to 50 ${\mu}m$. In order to show 1) that the effects of dopamine were mediated by dopamine receptors rather than by direct action on ionic channels and 2) which type of dopamine receptor might be responsible for the various effects, we assayed the ability of mammalian dopamine receptor antagonists, SCH-23390 (antagonist of D1 receptor) and spiperone (antagonist of D2 receptor), to block the dopamine-dependent changes. The D1 and D2 antagonists partially inhibited the dopamine-dependent hyperpolarization and the decrease in action potential amplitude. They both completely blocked the decrease in action potential duration and the increase in action potential after-hyperpolarization. The dopamine-induced slowdown of the depolarization in the initial phase of the action potentials was less effected by SCH-23390 and spiperone. From the results we suggest 1) that Helix F-lobe neurons may have a single type of dopamine receptor that binds both SCH-23390 and spiperone and 2) that the dopamine receptor of Helix F-lobe neurons may be homologous with and primitive to the family of mammalian dopamine receptors.

• 대한약리학회지
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• 제24권1호
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• pp.135-145
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• 1988

Dopamine(DA)은 뇌실내 투여시에 항이뇨와 함께 Na 배설증가 경향을 보이며, $D_1$, 및 $D_2$ 두 종류의 중추 Dopamine수용체가 신장기능에 서로 상반되는 영향을 미치고 있음이 시사된 바 있다. 본 연구에서는 선택적 $D_2$ 길항제인 Comperidone(DOM)을 이용하여 중추 $D_2$ 수용체의 역할을 구명코자 하였다. DOM은 측뇌실내로 (icv)투여시 항이뇨 및 Na 배설감소를 초래하였으며 신혈류 및 사구체여과율도 감소하였다. 전신혈압은 약간 증가하였다. 정맥내투여시에는 Na 배설에 변동이 없었다. 신경을 제거한 신장에서는 icv DOM에 의한 신혈류역학적 변동은 제거되었으나 Na 배설은 제신경신장측에서도 정상신장측에서와 같이 감소하였다. DA icv의 항이뇨작용은 DOM 전처치에 의하여 영향받지 아니하였다. $D_2$ 수용체 agonist인 Bromocriptine은 뇌실내 투여시 현저한 이뇨 및 Na 이뇨를 나타냈으나 이 작용은 DOM 전처치로 완전히 차단되었다. 또 다른 형의 $D_2-agonist$인 Apomorphine의 icv 투여는 일과성으로 신혈류역학의 증가와 함께 이뇨 및 Na 배설증가를 초래하였으며, DOM 전처치는 신혈류역학변동에 영향을 주지 못하였으나 뇨량 및 Na배설증가는 DOM 전처치에 의하여 현저하게 감약시켰다. 본 연구는 중추 $D_2$ 수용체가 어떤 체액성 natriuretic factor를 퉁하여 신장에 이뇨 및 Na 배설증가작용을 미치고 있음을 시사하였으며, 중추 $D_1$, 수용체는 신경경로를 통하여 항이뇨적 영향을 미치고 중추 $D_2$ 수용체는 Na 배설증가작용을 매개한다는 가설을 뒷받침하는 증거를 제시하였다.

• Biomolecules & Therapeutics
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• 제27권6호
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• pp.514-521
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• 2019

G protein-coupled receptors (GPCRs) are membrane receptors whose agonist-induced dynamic conformational changes trigger heterotrimeric G protein activation, followed by GRK-mediated phosphorylation and arrestin-mediated desensitization. Cytosolic regions of GPCRs have been studied extensively because they are direct contact sites with G proteins, GRKs, and arrestins. Among various cytosolic regions, the role of helix 8 is least understood, although a few studies have suggested that it is involved in G protein activation, receptor localization, and/or internalization. In the present study, we investigated the role of helix 8 in dopamine receptor signaling focusing on dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R). D1R couples exclusively to Gs, whereas D2R couples exclusively to Gi. Bioinformatic analysis implied that the sequences of helix 8 may affect GPCR-G protein coupling selectivity; therefore, we evaluated if swapping helix 8 between D1R and D2R changed G protein selectivity. Our results suggest that helix 8 is not involved in D1R-Gs or D2R-Gi coupling selectivity. Instead, we observed that D1R with D2R helix 8 or D1R with an increased number of hydrophobic residues in helix 8 relative to wild-type showed diminished ${\beta}$-arrestin-mediated desensitization, resulting in increased Gs signaling.