• Biomedical Science Letters
• /
• v.18 no.3
• /
• pp.218-226
• /
• 2012

Dopamine is an enteric neurotransmitter that regulates gastrointestinal motility. This study was done to investigate whether dopamine modulates spontaneous pacemaker activity in cultured interstitial cells of Cajal (ICCs) from mouse using whole cell patch clamp technique, RT-PCR and live $Ca^{2+}$ imaging analysis. ICCs generate pacemaker inward currents at a holding potential of -70 mV and generate pacemaker potentials in current-clamp mode. Dopamine did not change the frequency and amplitude of pacemaker activity in small intestinal ICCs. On the contrary dopamine reduced the frequency and amplitude of pacemaker activity in large intestinal ICCs. RT-PCR analysis revealed that Dopamine2 and 4-receptors are expressed in c-Kit positive ICCs. Dopamine2 and 4 receptor agonists inhibited pacemaker activity in large intestinal ICCs mimicked those of dopamine. Domperidone, dopamine2 receptor antagonist, increased the frequency of pacemaker activity of large intestinal ICCs. In $Ca^{2+}$-imaging, dopamine inhibited spontaneous intracellular $Ca^{2+}$ oscillations of ICCs. These results suggest that dopamine can regulate gastrointestinal motility through modulating pacemaker activity of large intestinal ICCs and dopamine effects on ICCs are mediated by dopamine2 receptor and intracellular $Ca^{2+}$ modulation.

• Korean Journal of Biological Psychiatry
• /
• v.2 no.1
• /
• pp.57-62
• /
• 1995

Objects : Clozapine, prototype of the atypical neuroleptics, was known to have unique antipsychotic effect with a few extrapyramidal effects. While most typical antipsychotic agents mainly block $D_2$ receptors, clozapine has higher affinity for dopamine $D_4$ receptor than for $D_2$ receptor. Many researchers have tried to find out the relationship between schizophrenia and the abnormality of the genes coding dopamine receptors. But no consistent findings were reported. Recently, dopamine $D_4$ receptor was fully sequenced, and the alleles of dopamine $D_4$ receptor gene was found in unusual form on the 48th base pair. Our study was performed to identify the distribution of the dopamine $D_4$ receptor alleles of schizophrenics and normal controls, and whether any difference between the dopamine $D_4$ receptor alleles of schizophrenics and that of normal controls exists. Methods : DNA was extracted from the blood of schizophrenic patients(N=60) and normal controls(N=60). Part of the dopamine $D_4$ receptor gene was amplified by PCR, and amplified DNA was electrophoresed. Authors compared the distribution of the alleles of dopamine $D_4$ receptor gene of normal controls and that of schizophrenic patients. Results : Six kinds of alleles of $D_4$ receptor were observed both groups. The fourth repeat form of alleles was the most common in both schizophrenic patients(75.8%) and normal controls(70.3%), so there was not significant difference between two groups. Conclusion : The Difference in the distribution of the dopamine $D_4$ receptor gene alleles is not thought to be responsible for the pathophysiology of the schizophrenia. However, the difference in the expression of the dopamine $D_4$ receptor gene between normal and schizophrenia is left to be scrutinized.

• Archives of Pharmacal Research
• /
• v.14 no.2
• /
• pp.109-113
• /
• 1991

Two types of aggressive behavior were produced by selective breeding in ICR mimce. NC900 line mice exhibited high level of species-typical, isolation-induced aggression, conversely, NC100 line mice exhibited little aggression. The present study tested the hypothesis that these differences involved brain monoamine systems. Comparisons of microdissected samples from various brain regions showed that NC100 line mice had significantly lower concentrations of dopamine. DOPAC and HVA in the nucleus accumbens (NAB) and caudate nucleus (NCU) than NC900 line. Homogenate binding studies demonstrated that NC100 mice had significantly increased density of $D_1$ dopamine receptor, but not $D_2$ dopamine receptor in the caudate nucleus. These results support the hypothesis that central dopamine pathways play an important role in modulating the genetically selected differences in aggressive behavior, and of which intensity differs from TEX>$D_1$\;and\;$D_2$ dopamine receptors.

• Korean Journal of Biological Psychiatry
• /
• v.9 no.1
• /
• pp.15-24
• /
• 2002

Even though alcoholism is a multi-factorial psychiatric disorder, it is reasonable to suppose that genetic factors play a substantial role in the manifestation of this disorder. Because alcohol is the reinforcing substance which manifests its effects through activation of the mesolimbic dopaminergic reward pathway of the brain, the gene encoding dopamine receptor subtypes can be a major natural candidate gene. Since 1990, many association studies have identified strong evidence implicating the dopamine D2 receptor(DRD2) gene in alcoholism, specifically TaqI A minor(A1) allele. Association studies have also been conducted on other dopamine receptor(DRD3 & DRD4) polymorphisms but the results have yet to be confirmed. Through a number of other approaches, each dopamine receptor gene has been investigated in association with different phenotypes in alcoholism, but further researches will be needed. In conclusion, studies in the past decade have shown that the TaqI A1 allele of the DRD2 gene is associated with alcoholism in various subject groups. Other dopamine receptor genes have since been added to the list but yet to be identified. Thus, the knowledge of these genes and their functional significance will enhance the understanding of the underlying biological mechanisms of alcoholism. Furthermore, it could lead to more helpful prevention and treatment approaches to alcoholism.

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

• Archives of Pharmacal Research
• /
• v.25 no.2
• /
• pp.202-207
• /
• 2002

This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a $GABA_A$ agonist, on the morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a reverse tolerance to the hyperactivity caused by morphine (10 mg/kg ,s.c.). THIP inhibited the development of reverse tolerance in the mice that had received the repeated same morphine (10 mg/kg s.c.) doses. The postsynaptic dopamine receptor supersensitivity, which was evidenced by the enhanced ambulatory activity its after the administration of apomorphine (2 mg/kg s.c.), also developed in the reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity indulged by the chronic morphine administration. These results suggest that the hyperactivity, reverse toterance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the $GABA_A$ receptors.

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

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.270.1-270.1
• /
• 2002

The signaling pathway of D2 dopamine receptor was studied using yeaslt two-hybrid system.. The 3rd cytoplasmic loop of rat D2 dopamine receptor was used to screen the cDNA library of mouse brain. and ALY was found to interact with it. The interaction in the yeast was observed only with the 3rd cytoplasmic loop of D2 dopamine receptor but not with that of D3 or D4 dopamine receptor. The interaction between two proteins was also confirmed by GST pull-down assay. (omitted)

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.89.1-89.1
• /
• 2003

The signaling pathway of dopamine D$_2$ receptor was studied using yeast two-hybrid system. The 3rd cytoplasmic loop of rat D$_2$ receptor was fond to interact with ALY. The interaction in the yeast was observed only with the 3rd cytoplasmic loop of D$_2$ receptor but not with that of D$_3$ or D$_4$ dopamine receptor. The interaction between two proteins was also confirmed by GST pull-down assay. Co-expression of D$_2$ receptor and ALY enhanced the expression of Lef-1 promoter in C6 cells and the promoter of D$_2$ dopamine receptor itself.

• Korean Journal of Biological Psychiatry
• /
• v.4 no.2
• /
• pp.218-224
• /
• 1997

The results regarding an association between the polymorphism sites in the dopamine $D_1$ receptor gene and schizophrenia compelled us to study the distribution of the polymorphism in Korean schizophrenia and controls. Eighty-eight schizophrenic patients and normal controls were examined by case-control study for distribution of the polymorphism of the dopamine $D_1$ receptor gene in Korean popualtion to minimize the effect of racial differencies in gene frequencies. The frequencies of the $B_1$ and $B_2$ in schizophrenic patients were 0.11 and 9.89, respectively. And 0.10 and 0.90 in normal control. Ther was no significant differences in the frequencies in the allele $B_1$ and $B_2$between schizophrenic patients and normal controls. The author present here the evidence of a lack of alleic association between the polymorphism of the dopamine $D_1$ receptor gene and Korean schizophrenic patients. The assumption that the dopamine $D_1$ receptor gene has a genetic role in the development of schizophrenia was not suppoorted by this case-control study.