• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.147-151
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• 2009

Repeated psychostimulants induce electroencephalographic (EEG) changes, which reflect adaptation of the neural substrate related to dopaminergic pathways. To study the role of dopamine receptors in EEG changes, we examined the effect of apomorphine, the dopamine D1 receptor antagonist, SCH-23390, and the D2 receptor antagonist, haloperidol, on EEG in rats. For single and repeated apomorphine treatment groups, the rats received saline or apomorphine for 4 days followed by a 3-day withdrawal period and then apomorphine (2.5 mg/kg, i.p.) challenge after pretreatment with saline, SCH-23390, or haloperidol on the day of the experiment. EEGs from the frontal and parietal cortices were recorded. On the frontal cortex, apomorphine decreased the power of all the frequency bands in the single treatment group, and increased the theta (4.5 ${\sim}$ 8 Hz) and alpha (8 ${\sim}$ 13 Hz) powers in the repeated treatment group. Changes in both groups were reversed to the control values by SCH-23390. On the parietal cortex, single apomorphine treatment decreased the power of some frequency bands, which were reversed by haloperidol but not by SCH-23390. Repeated apomorphine treatment did not produce significant changes in the power profile. These results show that adaptation of dopamine pathways by repeated apomorphine treatment could be identified with EEG changes such as increases in theta and alpha power of the frontal cortex, and this adaptation may occur through changes in the D1 receptor and/or the D2 receptor.

• The Korean Journal of Physiology
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• 제17권2호
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• pp.103-107
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• 1983

This experiment was undertaken to see whether dopamine has any effect on a uterine function and whether the uterus has a dopamine receptor. We used 14 female rats in the diestrus state which was identified by a vaginal smear. Under ether anesthesia, 3 pieces(1 cm length) from each side of the uterus were dissected out and mounted in 3 tissue chambers (4 cm diameter, 10 cm height) that contained Krebs-Ringer solution. The solution was continuously aerated with 95% $O_2$ containing 5% $CO_2$ and kept $37^{\circ}C$ consistantly during the whole experimental period. The spontaneous contractile activity of the isolated uterus was recorded using a force transducer. After a recovery period of 15 min in the chamber, the following experiments were carried out. In 7 rats, each piece of the uterus was received dopamine at concentrations of $10^{-4}$, $10^{-5}$ or $10^{-6}\;M$ for 10 min and then followed by domperidone at a concentration of $10^{-5}\;M$. In another 7 rats, each piece was received domperidone, a specific peripheral dopamine receptor antagonist, was administered at a concentration of $10^{-5}\;M$ for 5 min prior to dopamine at concentrations of $10^{-4}$, $10^{-5}$, or $10^{-6}\;M$. Dopamine inhibited the spontaneous uterine contraction dose-dependently (r=0.99, p<.01). The inhibited contractility by dopomine was significantly (P<.05) resumed by post-treatment of domperidone. Pre-treatment of domperidone also blocked significantly(p<.05) the inhibitory effect of dopamine. It is concluded from these results that dopamine has inhibitory role upon the spontaneous uterine contraction of the rat in the diestrus state and domperidone antagonized the inhibitory effect of dopamine. These results suggest strongly that dopamine may exert the inhibitory effect via the dopamine receptor in the rat uterus.

• 생물정신의학
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• 제7권2호
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• pp.159-163
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• 2000

Background : Dopamine receptors are strong candidates for involvement in schizophrenia and are target of a wide variety of antipsychotics. Dopamine $D_5$ receptor(DRD5) gene polymorphisms may be associated with various treatment response. The purpose of our study was define to what significance can be held as a predictor of treatment response in this polymorphism. Method : The total number of 116 Korean chronic schizophrenic patients was assessed after 48 weeks treatment. The Positive and Negative Syndrome Scale(PANSS) was rated for the clinical response to various antipsychotics. With the use of polymerase chain reaction amplification, we assessed this dopamine $D_5$ receptor polymorphism in schizophrenic patients who had been treated with antipsychotics, and related genotype with treatment response, to test the hypothesis that DRD5 polymorphism may lead to varying response to antipsychotics. Result : DRD5 polymorphism was not associated with treatment response to a variety of antipsychotics in chronic schizophrenic patients. Conclusion : Genetic variation of $D_5$ receptors do not predict treatment response to antispychotics.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10339-10343
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• 2015

Breast cancer is the most common cancer among females worldwide and a most prevalent malignancy in Iranian women. Chronic stress may make an important contribution to cancer, especially in the breast. Numerous studies showed roles of neurotransmitters in the occurrence and progression of cancers which are mediated by their various types of receptors. This study was conducted to evaluate alterations in the expression profile of dopamine receptor genes in peripheral blood mononuclear cells (PBMC) as stress factors in breast cancer patients and the human breast cancer cell line (MCF-7). Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total mRNA was extracted from PBMC and MCF-7 cells and RT-PCR was performed to confirm the presence of five dopamine receptors (DRD1-DRD5). Expression changes of dopamine receptor genes were evaluated by real time PCR. We observed that DRD2-DRD4 in PBMCs of breast cancer patients were increased compared to healthy individuals. In addition, all dopamine receptor subtypes but DRD1 were expressed in MCF-7 cells. Therefore, alterations of these receptors as stress factors should be assessed for selecting appropriate drugs such as D2-like agonists for treatment of breast cancer after performing complimentary tests. Determining the expression profile of dopamine receptor genes thus seems promising.

• Animal cells and systems
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• 제3권2호
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• pp.103-113
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• 1999

Many in-depth reviews related to regulations of prolactin secretion are available. We will, therefore, focus on controversial aspects using personal opinion in this review. The neuroendocrine control of prolactin secretion from the anterior pituitary gland involves multiple factors including prolactin-release inhibiting factor (PIF) and prolactin releasing factor (PRF). The PIF exerts a tonic inhibitory control in the physiological conditions. The PIF should be able to effectively inhibit prolactin release or a lifetime, but the inhibitory action of dopamine cannot be sustained for a long period of time. Perifusion of a high concentration of dopamine (l ,000 nM) could not sustain inhibitory action on prolactin release but when a small amount of ascorbic acid (0.1 mM) is added in a low concentration of dopamine (3 nM) solution, prolactin release was inhibited for a long period. Ascorbate is essential for dopamine action to inhibit prolactin release. We have, therefore, concluded that the PIF is dopamine plus ascorbate. The major transduction system for dopamine to inhibit prolactin release is the adenylyl cyclase system. Dopamine decreases cyclic AMP concentration by inhibiting adenylyl cyclase, and cyclic AMP stimulates prolactin release. However, the inhibitory mechanism of dopamine on prolactin release is much more complex than simple inhibition of CAMP production. The dopamine not only inhibits cyclic AMP synthesis but also inhibits prolactin release by acting on a link(s) after the CAMP event in a chain reaction for inhibiting prolactin release. Low concentrations of dopamine stimulate prolactin release. Lactotropes are made of several different subtypes of cells and several different dopamine receptors are found in pituitary. The inhibitory and stimulatory actions induced by dopamine can be generated by different subtype of receptors. The GH$_4$ZR$_7$ cells express only the short isoform (D$_{2s}$) of the dopamine receptor, as a result of transfecting the D$_{2s}$ receptors into GH$_4$C$_1$ cells which do not express any dopamine receptors. When dopamine stimulates or inhibits prolactin release in GH$_4$ZR$_7$ cells, it is clear that the dopamine should act on dopamine D$_{2s}$ receptors since there is no other dopamine receptor in the GH$_4$ZR$_7$. Dopamine is able to stimulate prolactin release in a relatively low concentration while it inhibits in a high concentration in GH$_4$ZR$_7$. These observations indicate that the dopamine D$_2$ receptor can activate stimulatory and/or inhibitory transduction system depending upon dopamine concentrations.

• Biomolecules & Therapeutics
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• 제24권5호
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• pp.517-522
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• 2016

${\beta}$-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of ${\beta}$-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with ${\beta}$-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with ${\beta}$-arrestin2. For this, we employed dopamine $D_2$ and $D_3$ receptors ($D_2R$ and $D_3R$, respectively), since they display distinct agonist-induced interactions with ${\beta}$-arrestins. Our results showed that the second and third intracellular loops of $D_2R$ are involved in the agonist-induced translocation of ${\beta}$-arrestins toward plasma membranes. In contrast, the N- and C-termini of $D_2R$ exerted negative effects on the basal interaction with ${\beta}$-arrestins.

• 약학회지
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• 제45권2호
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• pp.205-213
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• 2001

The dopaminergic receptors were consisted of two distinct subtypes, $D_1$and $D_2$, each having different function. The present study was attempted to investigate the effects of R(-)-2,10,11-trihydroxy-N-n-propylnoraporphine (TNPA), a dopamine $D_2$receptor agonist, on renal function in dog. TNPA (5.0~15.0 $\mu$g/kg), when given into the vein, produced a dose-dependently antidiuresis along with the decrease in osmolar clearance ( $C_{osm}$) and urinary excretion of sodium and potassium ( $E_{Na}$ , and $E_{K}$). It also increased reabsorption rates of sodium and potassium in renal tubules ( $R_{Na}$ , $R_{K}$) without any changes in glomerular filtration rate (GFR), renal plasma flow (RPF) and free water clearance ( $C_{H2o}$). TNPA (0.5~1.5 $\mu$g/kg/min) infused into a renal artery decreased urine flow both in the experimental and the control kidneys. TNPA (1.5~5.0 $\mu$g/kg) administered via the carotid artery also greatly exhibited antidiuresis even at intravenously ineffective doses. Changes of renal function by TNPA given into both the renal artery and the carotid artery were almost the same aspect to those induced by intravenous TNPA. These results obtained from the present study suggest that TNPA produces antidiuresis by increasing the reabsorption rates of electrolytes in renal tubules, mainly distal tubule, through changing of central function.unction.

• Biomolecules & Therapeutics
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• 제30권2호
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• pp.191-202
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• 2022

Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D₂ receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D₂ receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.

• 생물정신의학
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• 제3권1호
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• pp.51-56
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• 1996

The effects of 3 week treatment with haloperidol(2mg/kg/day, i.p.) on dopamine(DA) D2 receptor and DA metabolism in rat striata were studied at various time points after withdrawal from the drug treatment. Striatal DA D2 receptors were characterized with the radioligand 0.5nM [$^3H$]Spiperone. Dopamine(DA), homovanillic acid(HVA), 3,4-dihydroxyphenyl acetic acid(DOPAC) in rat striatum were measured with the high performance liquid chromatography. Drug withdrawal for 1 week induced significant increase in the number of D2 receptor in striatum after withdrawal for 1 week(p<0.05), and then this change was restored to control level during the withdrawal time of 2 and 4 weeks. There was no difference in striatal concentrations of DA and its metabolites among the groups. In conclusion, one-week withdrawal from chronic haloperidol treatment induced DA D2 receptor supersensitivity in the striatum, and that was normalized rapidly. Though this adaptive change in DA receptors, it may not affect the metabolism of DA in striatum.

• The Korean Journal of Physiology and Pharmacology
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• 제11권4호
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• pp.139-144
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• 2007

Recent studies suggest that alterations in glutamate receptor subunit levels in mesocorticolimbic dopamine areas could account for neural adaptations in response to psychostimulant drugs. Although many drugs of abuse induce changes in ionotropic glutamate receptor subunits in mesocorticolimbic dopamine areas, the changes of ionotropic glutamate receptor subunits by repeated nicotine treatment in these areas are not known. To answer this question, we injected male Sprague-Dawley rats twice daily with nicotine (0.4 mg/kg) or saline (1 ml/kg) for 10 days. The immunoreactivity of NR1, GluR1, and GluR2 glutamate receptor subunits was examined $16{\sim}18 h$ after the last injection of saline or nicotine. Repeated nicotine treatment significantly increased NR1 levels in the ventral tegmental area (VTA). In addition, repeated nicotine treatment showed a tendency towards an increase in GluR1 levels in the VTA as well as in striatum. However, there was no significant change in glutamate receptor subunits in other areas including nucleus accumbens (NAc). These results demonstrate that repeated nicotine treatment increases NR1 levels in VTA similarly to other drugs of abuse, suggesting that elevated glutamate receptor subunits in the VTA, but not NAc may be involved in the excitation of mesocorticolimbic dopamine neurons by nicotine.