• Title/Summary/Keyword: dopamine receptor

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Three-dimensional Pharmacophore Mapping of a Series of Isoxazolylpiperazine Inhibitors Selectively acting on the Dopamine D4 Receptor

  • Pae, Ae-Nim;Lee, In-Young;Koh, Hun-Yeong
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.183-185
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    • 2002
  • The discovery of new ligands with affinity and selectivity for the dopamine $D_2$ receptor subtypes is an important area in medicinal chemistry. The distribution of the $D_2$ receptors in the limbic areas of brain suggests that these receptors may be particularly an attractive target for the design of potential selective antipsychotic drugs without causing extrapyramidal side effects. (omitted)

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The Inhibitory Effect of Dopamine on Myoblast Fusion in vitro (Dopamine의 배양근원세포 융합억제 작용)

  • Kang, Man-Sik;Song, Woo-Keun;Song, Yung-Kook
    • The Korean Journal of Zoology
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    • v.29 no.4
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    • pp.235-244
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    • 1986
  • In order to elucidate the effect of neurotransmitter on the differention of myoblasts in vitro, dopamine was administered to the myoblasts at varying stages of myogenesis, and the fusion index, the rate of creatine kinase (CK) synthesis, and the sensitivity to dopamine were determined. When dopamine $(3 \\times 10^{-5} M)$ was administered at 34 hr after myoblast seeding, a significant decrease in the fusion index as well as CK synthesis was observed, indicating a good correlation exists between these two parameters. In other experiment, dopamine was administered at varying stages of myogenesis and the inhibitory effect of dopamine as scored by fusion index at 96 hr was found to be cyclic in nature. This finding raised a possibility that arrangement of dopamine receptors occurs according to the cell cycle stages in myogenesis.

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Effects of Dopamine on the Contractility and Action Potential of the Rabbit Papillary Muscle (Dopamine이 토끼 유두근의 수축력과 활동전압에 미치는 영향)

  • Huh, In-Hoi;Park, Jong-Wan
    • YAKHAK HOEJI
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    • v.32 no.6
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    • pp.402-414
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    • 1988
  • In order to clarify the receptor types and mechanisms underlying the positive inotropic effect of dopamine on the mammalian ventricular myocardium, the action potential, its first derivatives and isometric contraction of the rabbit papillary muscle were recorded using a force transducer and glass capillary microelectrodes filled with 3M KCl. The results were as follows; (1) In normal Tyrode solution, the contractile force was increased and duration of action potential was shortened with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (2) The dose-response curve was markedly shifted to the right by pretreatment with reserpine (5mg/kg i.p., 24hrs prior to the experiment). (3) In 19mM $K^+-Tyrode$ solution, the duration of action potential, maximum rate of rise (V_{max}) of action potential and overshoot were significantly increased with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (4) The inotropic effect of dopamine on the rabbit papillary muscle pretreated with reserpine was antagonized by atenolol ($10^{-6}M$), but not by phentolamine ($3{\times}10^{-6}M$). (5) In rabbit papillary muscle partially depolarized by 19mM $K^+-Tyrode$ solution, slow electrical response (calcium mediated action potential) as well as contraction were restored by dopamine ($10^{-4}M$); this restoration was blocked by calcium antagonists ($3{\times}10^{-5}M$ $LaCl_3{\cdot}6H_2O$, $3{\times}10^{-6}M$ diltiazem) or ${\beta}-adrenoceptor$ antagonist ($3{\times}10^{-6}M$ atenolol), but not affected by ${\alpha}-adrenoceptor$ antagonist ($10^{-5}M$ phentolamine, $3{\times}10^{-6}M$ yohimbine) or vascular dopaminergic receptor antagonist ($10^{-5}M$ haloperidol). The above results may be interpreted as that the positive inotropic effect of dopamine through both direct and indirect action are caused by increase in slow inward current ($Ca^{2+}$ influx into themyocardial cell), and the direct action is mainly due to the stimulation of ${\beta}-adrenoceptors$ in the rabbit papillary muscle.

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Inhibition by MK-801 of Morphine-Induced Conditioned Place Preference and Postsynaptic Dopamine Receptor Supersensitivity in Mice

  • Kim, Hack-Seang;Park, Woo-Kyu;Jang, Choon-Gon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.214-214
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    • 1996
  • Intraperitoneal injection of morphine (5 mg/kg) in mice every other day for 8 days produced conditioned place preference (CPP). CPP effects were evaluated by assessing the difference in time spent in the drug-paired compartment and the saline-paired compartment of the place conditioning apparatus. The injection of a non-competitive NMDA antagonist, MK-801 (0.05 and 0.1 mg/kg, i.p.), prior to and during morphine treatment in mice Inhibited morphine-induced CPP. The development of postsynaptic dopamine (DA) receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg). MK-801 inhibited that development of postsynaptic DA receptor supersensitivity MK-801 also inhibited apomorphine-induced climbing behavior, suggesting that MK-801 Inhibits dopaminergic activation mediated via the NMDA receptor.

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The Association between Polymorphism of the Dopamine D3 Receptors and Concentrations of Plasma Homovanillic and 5-hydroxyindoleacetic Acid, and Therapeutic Response of Chronic Schizophrenic Patients (만성 정신분열병 환자에서 도파민 D3 수용체 다형성 및 혈장 Homovanillic Acid와 5-hydroxyindoleacetic Acid 농도의 치료반응과의 연관)

  • Jeong, Geo Jang;Lee, Min Soo;Kim, Sang Yoon;Kang, Dae Yeop;Kwak, Dong Il
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.116-122
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    • 2001
  • Objectives : Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the $D_3$ receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response in chronic schizophrenic patients. Methods : Therapeutic response for 116 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). Results : Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. Conclusion : A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.

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Renal Action of Raclopride, a Dopamine $D_2$ Receptor Antagonist, in Dogs (Dopamine $D_2$ Receptor 차단제인 Raclopride의 신장작용)

  • 고석태
    • YAKHAK HOEJI
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    • v.45 no.6
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    • pp.683-693
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    • 2001
  • This study was attempted to investigate the effect of raclopride, a dopamine $D_2$ receptor antagonist, on renal function in dog. Raclopride (70-220$\mu\textrm{g}$/kg), when given intravenously, Produced antidiuresis along with the decrease in free water clearance ( $C_{H_2O}$), urinary excretion of sodium and potassium ( $E_{Na}$ , $E_{K}$), partially decreased osmolar clearance ( $C_{osm}$) and increased reabsorption rates of sodium and potassium in renal tubules ( $R_{Na}$ , $R_{K}$). Raclopride administered into a renal artery did not influence on renal function in small doses (10 and 30$\mu\textrm{g}$/kg), whereas exhibited the decrease of urine volume (Vol) and $C_{H_2O}$ both in experimental and control kidney in much dose (100$\mu\textrm{g}$/kg), at this time, the decreased rates of both Vol. and $C_{H_2O}$) were more prominent in control kidney rather than that elicited in experimental kidney, and then only via was decreased in control kidney but increased in experimental kidney. Raclopride administered via carotid artery (30-200$\mu\textrm{g}$/kg) did not influence at all on renal function. Antidiuretic action induced by raclopride given intravenously was not affected by renal denervation. Raclopride given into carotid artery was little effect on renal function without relation to renal denervation. Above results suggest that raclopride produces antidiuresis by potentiation of antidiuretic hormone (ADH) action in blood without increase of ADH secretion in posterior pituitary gland, it is not related to renal nerve function in dogs.ogs.s.

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Lesion of Subthalamic Nucleus in Parkinsonian Rats : Effects of Dopamine $D_1$ and $D_2$ Receptor Agonists on the Neuronal Activities of the Substantia Nigra Pars Reticulata

  • Park, Yong-Sook;Jeon, Mi-Fa;Lee, Bae-Hwan;Chang, Jin-Woo
    • Journal of Korean Neurosurgical Society
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    • v.42 no.6
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    • pp.455-461
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    • 2007
  • Objective : It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson's disease. The effects of SKF38393 (a $D_1$ receptor agonist) and Quinpirole (a $D_2$ receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. Methods : SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB+STN lesioned rats. Results : The administration of SKF38393 decreased SNpr neuronal firing rates and the percentage of burst neurons in the MFB lesioned rats, but did not alter them in MFB+STN lesioned rats. The administration of Quinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons. Conclusion : This study demonstrated that dopamine agonists and STN lesion decreased the hyperactive firing rate and the percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats, respectively. Quinpirole with STN lesion increased a percentage of burst neurons. To clear the exact interactive mechanism of $D_1$ and $D_2$ agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and $D_1$, $D_2$ selective antagonist.

Dopamine Modulates Corticostriatal Synaptic Transmission through Both $D_1$ and $D_2$ Receptor Subtypes in Rat Brain

  • Lee, Hyun-Ho;Choi, Se-Joon;Kim, Ki-Jung;Cho, Hyeong-Seok;Kim, Seong-Yun;Sung, Ki-Wug
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.5
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    • pp.263-268
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    • 2005
  • Striatum has important roles in motor control, habitual learning and memory. It receives glutamatergic inputs from neocortex and thalamus, and dopaminergic inputs from substantia nigra. We examined effects of dopamine (DA) on the corticostriatal synaptic transmission using in vitro extracellular recording technique in rat brain corticostriatal slices. Synaptic responses were elicited by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. Corticostriatal population spike (PS) amplitudes were decreased ($39.4{\pm}7.9$%) by the application of $100{\mu}M$ DA. We applied receptor subtype specific agonists and antagonists and characterized the modulation of corticostriatal synaptic transmission by different DA receptor subtypes. $D_2$ receptor agonist (quinpirole), antagonist (sulpiride), and $D_1$ receptor antagonist (SKF 83566), but not $D_1$ receptor agonist (SKF 38393), induced significantly the reduction of striatal PS. Pretreatment neither with SKF 83566 nor sulpiride significantly affected corticostriatal synaptic inhibition by DA. However, the inhibition of DA was completely blocked by pretreatment with mixed solution of both SKF 83566 and sulpiride. These results suggest that DA inhibits corticostriatal synaptic transmission through both $D_1$ and $D_2$ receptors in concert with each other.