• Journal of Genetic Medicine
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• v.2 no.1
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• pp.27-30
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• 1998

Previously, we made a study report on the genotype distribution and the gene frequency of angiotesin I-converting enzyme (ACE) in Korean population, and on the association between hypertension and genetic variance of ACE. This time, we have investigated a rapid mismatch-PCR/RFLP assays for the variant of the angiotesin II type 1 receptor ($AT_1R$) gene (an $A{\rightarrow}C$ transversion at position 1166 of $AT_1R$ gene), a mutation which may interact with the ACE polymorphism in the determining of risk of myocardial infarction. The genotype distributions of Koreans' angiotensin II type 1 receptor gene were AA (66.3%):AC (28.1%):CC (5.6%), thus the AA genotype was most numerous, and the allele frequency was A:C = 0.803:0.197. Genotype distributions were shown as AA (76.8%):AC (20.9%):CC (2.3%), the allele frequency was A:C = 0.872:0.128 in the male group, and AA (47.4%):AC (41.0%):CC (11.6%), A:C = 0.679:0.321 in the female group. Differences were highly significant between the male and female groups (p<0.0001). Genotype distributions between angiotensin II type 1 receptor gene and angiotensin converting enzyme gene showed that there is no significance between $AT_1R$ genotypes and ACE genotypes in total subjects (p>0.05).

• Journal of Yeungnam Medical Science
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• v.12 no.2
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• pp.246-259
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• 1995

This study aimed to investigate the mechanism of action of baclofen on the detrusor muscle isolated from rat. Rats (Sprague-Dawley) were sacrificed by decapitation and exsanguination. Horizontal muscle strips of $2mm{\times}15mm$ were prepared for isometric myography in isolated muscle chamber bubbled with 95% / 5%-$O_2$ / $CO_2$ at $37^{\circ}C$, and the pH was maintained at 7.4. Detrusor strips contracted responding to the electrical field stimulation (EFS) by 2 Hz, 20 msec, monophasic square wave of 60 VDC. The initial peak of EFS-Induced contraction was tended to be suppresed by ${\alpha},{\beta}$-methylene-adenosine 5'-triphosphate (mATP), a partial agonist of purinergic receptor, and baclofen, a $GABA_B$ receptor agonist (statistically nonsignificant). The late sustained contraction by EFS was suppressed significantly (p < 0.05) by additions of atropione, a cholinergic muscarinic receptor antagonist and baclofen. The adenosine 5'-triphosphate-induced contraction was completely abolished by mA TP but not by baclofen. In the presence of atropine, the subsequent addition of acetylcholine could not contract the muscle strips: but the addition of acetylcholine in the presence of baclofen evoked a contraction to a remarkable extent. These results suggest that in the condition of present study, the cholinergic innervation may play a more important role than the purinergic one, and baclofen suppresses the contractility of rat detrusor by the stimulation of the $GABA_B$ receptors to inhibit the release of neurotransmitter from the cholinergic nerve ending.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2805-2809
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• 2013

Objective: This study aimed at investigating whether the orphan nuclear receptor NR4A2 is significantly associated with clinicopathologic features and overall survival of patients with nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was performed to determine NR4A2 protein expression in 84 NPC tissues and 20 non-cancerous nasopharyngeal (NP) tissues. The prognostic significance of NR4A2 protein expression was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results: We did not find a significant association between total NR4A2 expression and clinicopathological variables in 84 patients with NPC. However, we observed that high cytoplasmic expression of NR4A2 was significantly associated with tumor size (T classification) (P = 0.006), lymph node metastasis (N classification) (P = 0.002) and clinical stage (P = 0.017). Patients with higher cytoplasmic NR4A2 expression had a significantly lower survival rate than those with lower cytoplasmic NR4A2 expression (P = 0.004). Multivariate Cox regression analysis analysis suggested that the level of cytoplasmic NR4A2 expression was an independent prognostic indicator for overall survival of patients with NPC (P = 0.033). Conclusions: High cytoplasmic expression of NR4A2 is a potential unfavorable prognostic factor for patients with NPC.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.119-123
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• 2012

In the present study, the antinociceptive profiles of $Agrimonia$ $pilosa$ $Ledeb$ extract were examined in ICR mice. $Agrimonia$ $pilosa$ $Ledeb$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Agrimonia$ $pilosa$ $Ledeb$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by $Agrimonia$ $pilosa$ $Ledeb$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. Our results suggest that $Agrimonia$ $pilosa$ $Ledeb$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Agrimonia$ $pilosa$ $Ledeb$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.14-40
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• 2002

15-Deoxy-${\Delta}^{12, 14}$-prostaglandin $J_2$ (15-deoxy-$PGJ_2$), a naturally occurring ligand activates the peroxisome proliferator-activated $receptor-{\gamma}(PPAR-{\gamma}$). Activation of $PPAR-{\gamma}$ has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-$PGJ_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-$PGJ_2$ (0.2 to 1.6 ${\mu}M$) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/ml). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-$PGJ_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-$PGJ_2$(0.8 ${\mu}M$) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-$PGJ_2$ on the expression of p38 MAP kinase and activation of AP-1, The promoting ability of 15-deoxy-$PGJ_2$ did not occur through $PPAR-{\gamma}$, as synthetic PPAR-${\gamma}$ agonist andantagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), $PPAR-{\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and $PGE_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of f 5-deoxy-$PGJ_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-$PGJ_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 single pathway may be important in the promoting activity of 15-deoxy-$PGJ_2$ cells.

• Toxicological Research
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• v.16 no.2
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• pp.141-146
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• 2000

Phthalate esters are used extensively as a plasticizer in the manufacture of plastic products such as PVC bags and medical devices. Recently, phthalate esters have been shown to induce endocrine system mediated responses. However. only a Jew studies have been conducted for estrogenic activity of phthalate esters. In this study estrogenic activities of seven phthalate esters. butyl benzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), di-n-butylphthalate (DBP), diethylphthalate (DEP), di-n-pentylphthalate (DPP), di-n-propylphthalate (DPrP) and dicyclohexylphthalate (DCHP), were examined in vitro using E-screen assay and competitive binding assay. From the E-screen assay, BBP. DEHP. DBP and DEP showed weak estrogenic activity at the concentration of 5 $\mu\textrm{M}$. The relative proliferative effect (RPE) and the relative proliferative potency (RPP) were 50~70% and 0.01%. respectively, when compared with 500 pM of 17$\beta$-estradiol (E2). In competitive binding assay with the rat uterine estrogen receptor (ER), BBP and DEP showed weak binding potency ［(l/$10^4$~1/$10^5$ of E2］ while DEHP and DBP scarcely bound to ER. These results suggest that some phthalate esters have weak estrogenic activities in vitro.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.355-359
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• 2000

Cocaine induces immediate early gene expression and behavioral changes by blocking dopamine transporters in the terminals of nigrostriatal neurons in the striatum. The pharmacological role of serotonin 2/1C (5HT2/1C) receptors in cocaine-induced expression of zif268 (NGFI-A, egr1 and Krox-24) mRNA, a member of the zinc finger, was investigated using quantitative in situ hybridization histochemistry in vivo. Behavioral alterations induced by cocaine were also monitored in relation with blockade of the receptors. Systemic injection of ritanserin (1 mg/kg, s.c.), a 5HT2/1C receptor antagonist, did not reverse behavioral alterations and zif268 mRNA gene expression induced by 15 mg/kg cocaine, i.p., in the dorsal and ventral striatum. These data indicate that ritanserin-sensitive 5HT2/1C receptors are not necessary for cocaine-induced behavioral alterations and zif268 mRNA gene expression in the striatum.

• Journal of fish pathology
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• v.14 no.1
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• pp.31-36
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• 2001

A novel clonidine binding sites were characterized in the intestinal membrane isolated from seawater eels, Anguilla japonica. The specific clonidine binding sites consisted of at least two classes, high affinity ($K_d=1.4{\pm}0.3$ nM n = 5) and low affinity ($K_d=175{\pm}34$ nM n = 5) sites. The specific binding of 2 nM [$^3H$]clonidine was most enhanced at $20^{\circ}C$ and pH 7.5, and reversed by unlabelled clonidine. Such binding was hardly inhibited by adrenaline, yohimbine or rauwolscine, indicating that most binding sites are distinct from $\alpha_2$-adrenoceptor. The specific clonidine binding sites was inhibited by various imidazoline/guanidinium drugs, indicating existence of imidazoline/guanidinium receptive sites (IGRS) or imidazoline receptors in the eel intestine. Competition experiments revealed that rank order to displace 2 nM [$^3H$]clonidine from their binding sites was as follows : guanabenz > cirazoline = naphazoline = UK14,304 = ST587 $\geq$ clonidine $\geq$ idazoxan = RX821002 = tolazoline > ST93 = oxymetazoline = amiloride = ST91 > yohimbine = efaroxan = rauwolscine $\geq$ adrenaline = ST567 = histamine = agmatine. Although physiological role of IGRS is not clear yet even in mammalian cell/tissues, eel intestine may be a good model to elucidate how the IGRS act in the cell and to decide what is the endogenous ligand for the IGRS.

• Journal of Korean Neurosurgical Society
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• v.29 no.7
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• pp.868-876
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• 2000

Objective : Parkinsonian rat models have generally been characterized by unilateral destruction of both the nigrostriatal pathway and the mesolimbic pathway using the neurotoxin 6-hydroxydopamine. The induction of contraversive turning by apomorphine in these models is thought to reflect the stimulation of supersensitive dopamine D2 receptor or receptor-mediated mechanisms in denervated neostriatum. The present study was undertaken to investigate the expression of dopamine D2 receptor in denervated striatum according to modalities of apomorphine(dopamine agonist) treatment after creating a hemiparkinsonian rat model in which there is 6-hydroxydopamine induced destruction of the unilateral dopaminergic nigrostriatal pathway. Methods : After making complete lesion in left side substantia nigra pars compacta(SNpc) by stereotactic injection of 6-hydroxydopamine into medial and lateral areas of SNpc, and confirming successful animal model by apomorphine induced contraversive turning behavior without recovery and complete destruction of ipsilateral SNpc with tyrosine hydroxylase immunostaining in 7th day after operation, 15 rats of parkinsonian model were studied with or without administration of apomorphine at varying doses and durations. According to the modalities of apomorphine treatment for 4 days, these rats were divided into 3 groups, as not-treated group, intermittently treated group and constantly treated group. For investigating the extent of the expression of dopamine D2 receptor in denervated striatum, immunohistochemical staining by dopamine D2 receptor antibody and Western blot were performed. Results : In the D2 receptor antibody immunohistochemical staining, the mean number of positive stained neurons was highest in not-treated group($20.5{\pm}1.14$) of 3 groups. In constantly treated group, the mean number of positive stained neurons was less($3.9{\pm}1.79$) than intermittently treated group(p<0.05). The Western blotting with the D2 receptor antibody revealed that expression of receptors was also highest in not-treated group and less in constantiy treated group than intermittently treated group. Conclusion : Dopamine D2 receptors in denervated striatum of parkinsonian rat models, which were not treated with apomorphine, revealed to be most highly expressed. And, according to doses and durations of apomorphine administration, desensitization of the receptor was more apt to develop with constant treatment than intermittent treatment. In clinical setting, the authors believe that, in long-term treated parkinsonian patients, desensitization of dopamine receptors due to chronic dopaminergic stimulation seems to be partially related to mechanisms of drug tolerance.

• Korean Journal of Veterinary Research
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• v.32 no.1
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• pp.41-49
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• 1992

Higenamine is an Aconiti tuber derived compound whose chemical structure is 1-(4'-hydroxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline containing catechol ring and tetrahydroisoquinoline nucleus in its own structure, both of which are well known to have agonistic effects on adrenergic receptors. Using guinea-pig atria(rich in ${\beta}_1$-receptor) and treachea(rich in ${\beta}_2$-receptor), we studied pharmacological actions of higenamine on these organs with special interest of its relevancy of ${\beta}$-receptor selectivity. In order to further clarify its pharmacological characteristics, the influncences of pretreatment of reserpine or cocaine were also investigated. The results were summarized as follows : 1. Higenamine had remarkable chronotropic, inotropic and bronchodilator effects in guinea-pig spontaneously beating right atria, left atria and trachea, in dose-dependent manners. 2. All of above actions were blocked competitively by propranolol, which shows nonselectivity of higenamine on ${\beta}$-receptor. $pA_2$ values of propranolol against higenamine were 7.93, 7.76 and 8.46 in guinea-pig right atria, left atria and treachea, respectively. 3. Reserpine pretreatment(5mg/kg, ip, 24h) did not show my decrease in pharmacological actions of higenamine, which suggests higenamine has direct action on ${\beta}$-receptor not via catecholamine release. 4. Cocaine pretreatment$(1{\mu}M)$ had no influence on pharmacological actions of higenamine in contrast with nor epinephrine, which suggests there is no neuronal uptake mechanism of higenamine in the studied organ preparations.