• The Korean Journal of Physiology and Pharmacology
• /
• v.11 no.5
• /
• pp.197-206
• /
• 2007

The aim of the present study was to investigate the effects of 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine(SKF81297), a selective agonist of dopaminergic $D_1$ receptor, on the secretion of catecholamines(CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal gland, and also to elucidate the mechanism involved. SKF81297($10{\sim}100{\mu}M$) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh(5.32 mM), high $K^+$(56 mM), DMPP($100{\mu}M$) and McN-A-343($100{\mu}M$). Also, in adrenal glands loaded with SKF81297($30{\mu}M$), the CA secretory responses evoked by Bay-K-8644($10{\mu}M$), an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid($10{\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase were also inhibited. However, in the presence of the dopamine $D_1$ receptor antagonist, (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7-ol(SCH23390, $3{\mu}M$), which is a selective antagonist of dopaminergic $D_1$ receptor, the inhibitory responses of SKF81297($30{\mu}M$) on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Collectively, these experimental results suggest that SKF81297 inhibits the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation(both nicotininc and muscarinic receptors) and membrane depolarization. This inhibitory of SKF81297 seems to be mediated by stimulation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that the presence of the dopaminergic $D_1$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

• Natural Product Sciences
• /
• v.22 no.4
• /
• pp.246-251
• /
• 2016

This study investigated the effects of (-)-sesamin on memory deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD). MPTP lesion (30 mg/kg/day, 5 days) in mice showed memory deficits including habit learning memory and spatial memory. However, treatment with (-)-sesamin (25 and 50 mg/kg) for 21 days ameliorated memory deficits in MPTP-lesioned mouse model of PD: (-)-sesamin at both doses improved decreases in the retention latency time of the passive avoidance test and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, improved the decreased transfer latency time of the elevated plus-maze test, reduced the increased expression of N-methyl-D-aspartate (NMDA) receptor, and increased the reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB). These results suggest that (-)-sesamin has protective effects on both habit learning memory and spatial memory deficits via the dopaminergic neurons and NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mouse model of PD, respectively. Therefore, (-)-sesamin may serve as an adjuvant phytonutrient for memory deficits in PD patients.

• The Korean Journal of Nuclear Medicine
• /
• v.38 no.4
• /
• pp.294-299
• /
• 2004

Purpose: Both human NIS and mutant $D_2R$ transgenes are proposed as reporting system in transplanted cell tracking. Using hepatoma cell lines, we constructed a dual reporter system containing human sodium-iodide symporter (hNIS) and dopamine 2 receptor ($D_2R$) and compared its characteristics. Materials and Methods: The recombinant plasmid ($pIRES-hNIS/D_2R$) was constructed with IRES (internal ribosome entry site) under control of the CMV promoter $pIRES-hNIS/D_2R$ was transfected to human hepatoma SK-Hep1 cell line with lipofectamine. HEP-ND ($SK-Hep1-hNIS/D_2R$) cells stably expressing hNIS and $D_2R$ was established by selection with G418 for two weeks. RT-PCR was performed to investigate the expression of both hNIS and $D_2R$ genes. The expressions of hNIS and $D_2R$ were measured by $^{125}I$ uptake assays and receptor binding assays. Specific binding of $D_2R$ to $[^3H]spiperone$ was verified by Scatchard plot with (+) butaclamol as a specific inhibitor. $K_d\;and\;B_{max}$ values were estimated. The correlation between hNIS and $D_2R$ expression was compared by using each clone. Results: Similar quantities of hNIS and $D_2R$ genes were expressed on HEP-ND as RT-PCR assays. HEP-ND cells showed 30 to 40 fold higher radioiodine uptakes than those of parental SK-Hep1 cells. $^{125}I$ uptake in HEP-ND cells was completely inhibited by $KClO_4$, a NIS inhibitor Specific binding to HEP-ND cells was saturable and the $K_d\;and\;B_{max}$ values for HEP-ND cells were 2.92 nM, 745.25 fmol/mg protein and 2.91nM, 1323 fmole/mg protein in two clones, respectively. The radioiodine uptake by hNIS activity and $D_2R$ binding was highly correlated. Conclusion: We developed a dual positron and gamma imaging reporter system of hNIS and $D_2R$ in a stably transfected cell line. We expect that $D_2R$ and hNIS genes can complement mutually as a nuclear reporting system or that $D_2R$ can be used as reporter gene when hNIS gene were used as a treatment gene.

• Korean Journal of Biological Psychiatry
• /
• v.2 no.1
• /
• pp.63-69
• /
• 1995

The effects of chronic treatment with haloperidol and sulpiride on the binding capacities of dopamine(DA) receptor were examined in rat striatum and olfactory tubercle. Additionally, the stereotypy scores were assessed after apomorphine administration. Rats were treated with haloperidol(0.5mg/kg/day) or sulpiride(40mg/kg/day) for four weeks. Apomorphine(0.5mg/kg) was injected after three-day washout from neuroleptics, and stereotypy scores were assessed. Haloperidol group showed high scores of stereotyped behavior in comparison with control and sulpiride groups. With control group, sulpiride group displayed similar stereotyped behaviors. Saturation analysis of the binding of [$^3H$]spiperone to striatal membranes showed that the Bmax of haloperidol and sulpiride groups increased significantly in comparison with that of control group. The $K_D$ decreased significantly after sulpiride treatment in striatum. Although sulpiride produces the same proliferation of DA receptor, the low stereotypy scores of sulpiride group indirectly suggest that sulpiride acts differently from haloperidol in brain DA system. The Bmax increased remarkably following both treatment with haloperidol and sulpiride in olfactory tubercle. Also, the increase in $K_D$ was significant after treatment with haloperidol and sulpiride in olfactory tubercle. Moreover, the $K_D$ of control group in olfactory tubercle was more than twice the $K_D$ of control group in striatum. The $K_D$ was 86.2 in striatum and 37.5 pM in olfactory tubercle. The present finding indicates that sulpiride also induces the proliferation of DA receptor in olfactory tubercle and may interact with some DA receptor subtype with high affinity profile. The different affinities of the control groups of striatum and olfactory tubercle suggest that striatal DA receptor subtypes labeled by [$^3H$]spiperone could differ from those of olfactory tubercle.

• Journal of Ginseng Research
• /
• v.38 no.4
• /
• pp.256-263
• /
• 2014

Background: Korean Red Ginseng (KRG) is known to have antianxiety properties. This study was conducted to investigate the anxiolytic effects of KRG extract (KRGE) during ethanol withdrawal (EW) and the involvement of the mesoamygdaloid dopamine (DA) system in it. Methods: Rats were treated with 3 g/kg/d of ethanol for 28 d, and subjected to 3 d of withdrawal. During EW, KRGE (20 mg/kg/d or 60 mg/kg/d, p.o.) was given to rats once/d for 3 d. Thirty min after the final dose of KRGE, anxiety-like behavior was evaluated in an elevated plus maze (EPM), and plasma corticosterone (CORT) levels were determined by a radioimmunoassay (RIA). In addition, concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the central nucleus of the amygdala (CeA) were also measured by high performance liquid chromatography (HPLC). Results: The EPM test and RIA revealed KRGE inhibited anxiety-like behavior and the over secretion of plasma CORT during EW. Furthermore, the behavioral effect was blocked by a selective DA D2 receptor (D2R) antagonist (eticlopride) but not by a selective DA D1 receptor (D1R) antagonist (SCH23390). HPLC analyses showed KRGE reversed EW-induced decreases of DA and DOPAC in a dose-dependent way. Additionally, Western blotting and real-time polymerase chain reaction (PCR) assays showed that KRGE prevented the EW-induced reductions in tyrosine hydroxylase (TH) protein expression in the CeA and TH mRNA expression in the ventral tegmental area (VTA). Conclusion: These results suggest that KRGE has anxiolytic effects during EW by improving the mesoamygdaloid DA system.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.5
• /
• pp.565-572
• /
• 1998

The present study was to evaluate the protective effects of bromocriptine, which is known as $D_2$ dopamine receptor agonist and used for the treatment of patients with Parkinson's disease (PD), on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro and in vivo. Lipid peroxidation product (malondialdehyde; MDA) produced by the administration of 6-OHDA was profoundly reduced following the treatment of bromocriptine in a dose-dependent manner in rabbit brain homogenate. Quinone formation by 6-OHDA autoxidation was also attenuated, and its effect was as potent as other antioxidants. Pretreatment of bromocriptine reduced the cytotoxicity of 6-OHDA on SH-SY5Y neuroblastoma cell lines dose-dependently. The loss of striatal dopamine and its metabolite, DOPAC (dihydroxyphenylacetic acid) as well as increase of MDA production caused by intrastriatal injection of 6-OHDA was significantly recovered following the treatment of bromocriptine. The present study clearly showed that bromocriptine had a protective action against 6-OHDA-induced neurotoxicity. These results suggest that bromocriptine has the antioxidant properties, which could be another advantage for delaying the progress of Parkinson's disease.

• Anxiety and mood
• /
• v.2 no.1
• /
• pp.45-49
• /
• 2006

Puropse : Disturbances of dopaminergic system might be related to the possible mechanism of panic disorder. This study was aimed to examine the association of DRD2 Taq 1 polymorphism and panic disorder. Methods : One hundred and fourteen patients with panic disorder (62 male (54.4%), mean age $40.96{\pm}0.11$ years) and 200 comparison subjects (114 male (57.0%), mean age $35.57{\pm}8.81$ years)were tested for DRD2 TaqI A polymorphism. We excluded panic patients with comorbid alcohol related disorders, bipolar disorders, and any kinds of psychotic disorders because there have been some reports about association of these disease and DRD2 TaqI A polymorphism. Results : There was significant difference in the frequency of the genotype in DRD2 polymorphism between patients and controls (${\chi}^2$=6.09, df=2, p=0.048). The A1+ allele (A1A1 and A1A2) frequency analysis also showed significant association (${\chi}^2$=4.08, df=1, p=0.043). In addition, we observed a more strong and specific association between panic disorder and the A1+ allele of the DRD2 TaqI polymorphism for men (${\chi}^2$=4.71, df=1, p=0.03), but not for women (${\chi}^2$=0.45, df=1, p=0.50). Conclusion : These results in our Korean sample suggest that the DRD2 TaqI A polymorphism may be associated with panic disorder. Furthermore, we found sex-specific association of DRD2 A1 allele with panic disorder.

• Biomolecules & Therapeutics
• /
• v.25 no.3
• /
• pp.239-248
• /
• 2017

Desensitization and acute tolerance are terms used to describe the attenuation of receptor responsiveness by prolonged or intermittent exposure to an agonist. Unlike desensitization of G protein-coupled receptors (GPCRs), which is commonly explained by steric hindrance caused by the ${\beta}$-arrestins that are translocated to the activated receptors, molecular mechanisms involved in the acute tolerance of GPCRs remain unclear. Our studies with several GPCRs and related mutants showed that the acute tolerance of GPCRs could occur independently of agonist-induced ${\beta}$-arrestin translocation. A series of co-immunoprecipitation experiments revealed a correlation between receptor tolerance and interactions among receptors, ${\beta}$-arrestin2, and $G{\beta}{\gamma}$. $G{\beta}{\gamma}$ displayed a stable interaction with receptors and ${\beta}$-arrestin2 in cells expressing GPCRs that were prone to undergo tolerance compared to the GPCRs that were resistant to acute tolerance. Strengthening the interaction between $G{\beta}{\gamma}$ and ${\beta}$-arrestin rendered the GPCRs to acquire the tendency of acute tolerance. Overall, stable interaction between the receptor and $G{\beta}{\gamma}$ complex is required for the formation of a complex with ${\beta}$-arrestin, and determines the potential of a particular GPCR to undergo acute tolerance. Rather than turning off the signal, ${\beta}$-arrestins seem to contribute on continuous signaling when they are in the context of complex with receptor and $G{\beta}{\gamma}$.

• Korean Journal of Biological Psychiatry
• /
• v.11 no.1
• /
• pp.26-32
• /
• 2004

Background:The dopaminergic genes have been implicated with some personality traits. Many recent studies indicated that there is a correlation between D2 dopamine receptor gene(DRD2) polymorphisms and the personality traits. The purpose of this study is to investigate a possible association between DRD2 gene (TaqI A, TaqI B) polymorphism and personality traits. Methods:The subjects were consisted of 173 blood-unrelated young female Koreans with a mean age(${\pm}SD$) of 13.88(${\pm}0.29$) years. These volunteers were recruited from one of the junior high schools in Seoul and were tested by the Korean version of the Temperament and Character Inventory(TCI). Genotyping of the DRD2 polymorphisms by PCR methods were carried out. Two DRD2 gene polymorphisms were classified and individually assessed as follows:TaqI A1+ vs A1-, TaqI B1+ vs B-. The associations between the TCI scores and TaqI A, TaqI B polymorphisms were assessed by Student's t-test. Results:In the 173 subjects, the allele frequencies of the DRD2 TaqI A1, TaqI B1 alleles ranged from 0.42 to 0.43, and these results are quite different from the ranges of 0.15-0.20 in the case of a Caucasian population. The genotype frequencies of DRD2(TaqI A1, TaqI B1) variants showed no significant deviation from the Hardy-Weinberg equilibrium. RD4(dependence vs. independence) of Cloninger's TCI, a sub-dimension of Reward Dependence, was significantly higher in the subjects having DRD2 less frequent alleles than those without these alleles. Conclusion:This study suggests that the female subjects carrying the less frequent DRD2 alleles exhibited higher reward-dependent personality trait compared to those without these alleles.

• Biomolecules & Therapeutics
• /
• v.17 no.1
• /
• pp.32-42
• /
• 2009

The purpose of the present study was to examine the effect of dihydrexidine, a full $D_1$ receptor agonist, on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland, and to establish its mechanism of action. Dihydrexidine (10-100 ${\mu}M$), perfused into an adrenal vein for 60 min, relatively produced dose- and time-dependent inhibition in the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Dihydrexidine itself did fail to affect basal CA output. Also, in adrenal glands loaded with dihydrexidine (30 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$), an activator of L-type $Ca^{2+}$ channels, cyclopiazonic acid (10 ${\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, and veratridine, an activator of voltage-dependent $Na+$ channels (10 ${\mu}M$), were also markedly inhibited, respectively. However, in the simultaneous presence of dihydrexidine (30 ${\mu}M$) and R (+)-SCH23390 (a selective antagonist of $D_1$ receptor, 3 ${\mu}M$), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory responses by dihydrexidinetreatment alone. In conclusion, these experimental results suggest that dihydrexidine significantly inhibits the CA secretion evoked by cholinergic stimulation (both nicotinic and muscarinic receptors) and membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of dihydrexidine may be mediated by inhibiting influx of both $Ca^{2+}$ and $Na^+$ into the cytoplasm as well as by suppression of $Ca^{2+}$ release from cytoplasmic calcium store through activation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells.