• Korean Journal of Biological Psychiatry
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• v.12 no.2
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• pp.107-113
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• 2005

Purpose:In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine $D_2$ receptor polymorphism in schizophrenic patients. Methods:The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine $D_2$ receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). Results:The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (${\chi}^2$(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. Conclusions:The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.

• YAKHAK HOEJI
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• v.45 no.4
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• pp.397-406
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• 2001

It has been demonstrated previously that R(-)-2,10,11-trihydroxy-N-n-propylnora porphine (TNPA), a dopamine D$_2$receptor agonist, produced the antidiuresis through changes of central friction in dog. This study was investigated about effects of renal denervation and raclopride, a dopamine D$_2$receptor antagonist, on the antidiuresis of TNPA in order to elicidate the mechanism involved in this central antidiuresis induced by TNPA. Antidiresis exhibited by TNPA given into the vein or into carotid artery was not influenced by renal denervation, whereas antidiuresis of TNPA administered into carotid artery was blocked almost perfectly by raclopride pretreated into carotid artery. From these observations it is concluded that central antidiuresis induced by TNPA is brought about through activation of dopamine D$_2$receptor localized in brain, not related to renal nerve activity.

• BMB Reports
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• v.28 no.3
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.97-97
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• 2001

This Study was attempted to investigate tile effect of dopamine, SKF 81297, a dopamine D$_1$-receptor agonist, and TNPA, a dopamine D$_2$-receptor agonist, on the blood pressure in rat. Dopamine exhibited the hypertensive action in proportion to the doses of 1.0, 3.0 arid 10.0 $\mu\textrm{g}$/kg i.v., these hypertensive action of dopamine was blocked significantly by SCH 23390, a dopamine D$_1$-receptor antagonist, on the other hand, more potentiated by raclopride, a dopamine D$_1$-receptor antagonist. SKF 81297 produced hypertensive action in a dose of 1.0 $\mu\textrm{g}$/kg i.v., wherease hypotensive action in proportion to administered doses 3.0 and 10.0 $\mu\textrm{g}$/kg i.v., these hypertensive action of SKF 81297 in a dose of 1.0 $\mu\textrm{g}$/kg i.v. was not influenced by SCH 23390 or raclopride, but hypotensive action of SKF 81297 in tile doses of 3.0 and 10.0 $\mu\textrm{g}$/kg i.v. was weakened significantly by SCH 23390, but more strenthened by raclopride. TNPA showed the hypotensive action in inverse proportion to administered doses of 1.0, 3.0 and 10.0 $\mu\textrm{g}$/kg i.v., these hypotensive action was reversed to hypertensive action in inverse proportion to the administered doses of TNPA by SCH 23390 and raclopride.

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.50-58
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• 2002

lt had been reproted previously that (${\pm}$)6-chloro-7,8-dihydroxy-1-phenyl 2,3,4,5-tetra-hydro -lH-3benzazepine (SKF 81297), dopamine $D_1$ receptor agonist, produced diuresis by both Indirect action through central function and direct action being induced in kidney. This study was attempted in order to examine the diuresis mechanism of such SKF 81297 Diuretic action of SKF 81297 given into the vein or the carotid artery was not affected by renal denervation, whereas diuretic action of SKF 81297 administered into a renal artery was blocked completely by renal denervation, and then diuretic action of SKF 81297 injected into carotid artery was inhibited by SCH 23390, dopamine $D_1$ receptor antagonist, given into carotid artery. Above results suggest that indirect diuretic action of SKF 81297 elicites through central dopamine $D_1$ receptor and direct diuresis in kidney by influence of renal nerves.

• Journal of Gastric Cancer
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• v.6 no.3
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• pp.132-138
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• 2006

Purpose: Dopamine is a neurotransmitter, but in the GIT, the roles of dopamine are a regulator of epithelial cell proliferation, an endogenous protective factor, and a regulator of stomach cancer cell proliferation. By using two different gastric-cancer cell lines, we assessed the effects of dopamine and dopamine receptors on the proliferation of human gastric-cancer cells. Materials and Methods: To assess the effects of dopamine and dopamine receptors on the proliferation of human gastric-cancer cells, we investigated cell proliferation and the expression of D1, D2L, and D2S receptor in two gastric-cancer cell lines, SNU 601 and KCU-C2. The effects of dopamine and dopamine receptors on the level of the cell proliferation were determined by staining with an A/H/E (acridine orange, hoechst and ethidium bromide) mixture. Results: After dopamine treatment, the cell viability was significantly decreased in SNU 601 cells (P<0.05) where the D2L receptor was absent, but not in KCU-C2 cells. After treatment with raclopride, a D2 receptor antagonist, dopamine-dose-dependent inhibition of cell proliferation was observed in SNU 601 cells (P<0.05). After treatment with SCH 23390, a D1 receptor antagonist, dopamine significantly increased ceil proliferation in KCU-C2 cells (P<0.05), but inhibited ceil proliferation in SNU 601 cells (no D2L receptor). Conclusion: The dopamine signal via the D1 or the D2S receptor inhibited proliferation of gastric-cancer cells, but that via the D2L receptor increased proliferation. These results suggest that the regulatory effects of dopamine in the gastric-cancer cell proliferation may be controlled by using dopamine receptors.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.568-576
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• 2024

Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase-3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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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.

• 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.

• Korean Journal of Veterinary Research
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• v.32 no.2
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• pp.165-173
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• 1992

The present study was carried out to investigate the effects of dopaminergic drugs and the role of specific dopamine(DA) receptors on the release of TSH, $T_4$ and $T_3$. Serum TSH levels (cold-induced, $4{^{\circ}C}$) were determined using RIA(radioimmunoassay) at 30 min after administration of dopamine agonists and antagonists. Serum $T_4$ and $T_3$ levels were detected after these dopaminergic drugs were administered subcutaneously twice a day for a week. The results of the study are summarized as follows : Apomorphine, a nonspecific DA receptor agonist, produced a dose-depedent decrease in serum TSH, $T_4$ and $T_3$ levels. However, only low doses (0.3, 1.0mg/kg) of SKF38393, a specific $D_1$-receptor agonist, produced a decrease in serum lelvels of TSH. I,Y171555, a specific $D_2$-receptor agonist, produced a dose dependent decrease in serum TSH, $T_4$ and $T_3$ levels. However, SCH23390, a specific $D_1$-receptor antagonist, produced a decrease except in serum T levels which were increased dose dependently. High doses (1.0, 3.0mg/kg) of sulpiride, a specific $D_2$-receptor antagonist, made a increase in the serum levels of TSH and $T_3$. The effects of dopaminergic drugs in serum TSH and $T_4$ levels was potentiated by the pretreatment of apomorphine. The overall results of this study suggest that the regulation of TSH, $T_4$ and $T_3$ secretion were mediated via specific $D_1$ and $D_2$ receptor.