• Archives of Pharmacal Research
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• v.19 no.5
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• pp.390-395
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• 1996

To investigate whether $AT_{1}$ receptor antagonists are acting by increasing endothelium-de-pendent and -independent relaxation of aortas in normotensive rats, $AT_{1}$ receptor antagonists, losartan and KR-30988, and angiotensin converting enzyme inhibitor, captopril, were orally administered for two weeks (50 mg/kg, b.i.d.). THe blood pressure, heart rate and body weight were not significantly changed by losartan, KR-30988 and captopril compared to the control group. In aortic preparations, the $pD_{2}$ of KR-30988 for ACh-induced relaxation was 8.33 $\pm$ 0.16, significantly (p <0.05) lower than that of control group $(7.71 \pm 0.15)$. ACh-induced relaxation was significantly increased on losartan-treated group (p<0.01) at $10^{-6}$ M of ACh, and in captopril-treated group (p<0.05) at the range of $10^{-7}$ -$10^{-5}$ M of ACh. The $pD_{2}$ values for histamine-induced relaxatio of losartan, KR-30988 and captopril were 5.57 $\pm$ 0.10, 5.85 $\pm$ 0.21 and 5.60 $\pm$ 0.01, respectively, with significant differences in all groups (p<0.01) compared to that of control group (5.13 $\pm$ 0.09). ACh-induced relaxations of aortic preparations were not changed by pretreatment of indomethacin ($10_{-5}$ M), and completely bolcked by pretreatment of L-NAME $(10_{-5}M)$ in all groups. Sodium nitroprusside-induced relaxations were not significantly changed by all drugs tested in this experiments. These results suggest that $AT_{1}$ receptor antagonists, losartan and KR-30988, enhance the endothelium-dependent relaxatio on aortic preparations through the release of, or increase sensitivity, to nitric oxide in nor-motensive rats.

• Korean Journal of Microbiology
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• v.25 no.1
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• pp.52-56
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• 1987

The evidences that Lam B protein of E. coli is used as a receptor for infections of bacteriophage N4 as well as bacteriophage lambda were obtained from the following experimental results. First, all of the isolated lambda resistant dlones possessing foreign DNA fragments in the plasmids were also resistant to bacteriophage N4, but not to bacteriophage $\phi$ 80, T4 and T7. Second, when the plasmid DNA was treated with various restriction enzymes and ligated to delete the total or a portion of the foreign DNA fragments, the deleted plasmids lost the resistant activities to lambda and N4, simultaneously. Third, after amplification of Lam B protein about 200 times by inducing the protein using maltose as a sole carbon source, the host E. coli became sensitive to both lambda and N4.

• Journal of Ginseng Research
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• v.25 no.2
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• pp.74-81
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• 2001

The effect of Korean Ginseng saponins (total saponin, PD saponin and PT saponin) on the serotonin type 3 receptor, which is known to be involved in nausea and vomiting following anticancer chemotherapy or the general anesthesia, was investigated. after in vitro transcribed recombinant serotonin type 3 receptor in the Xenopus laevis oocyte, classic two electrodes voltage clamp technique was used. All of ginseng saponins inhibited the response of the agonist, serotonin, on the serotonin type 3 receptor in a dose-dependent manner. PT saponin showed to have the inhibitory effect more than 2 times as potent as PD saponin. Total saponin shifted the serotonin dose response plot to the right (EC$\_$50/, 0.70$\pm$0.17 $\mu$M into 3.57$\pm$1.42 $\mu$M, and Hill coefficient, 2.14$\pm$0.60 into 1.52$\pm$1.00). Ginseng saponin did not change the reversal potential (∼0 mV) of serotonin type 3 receptor. These results suggest that Korean ginseng saponin may have the inhibitory effect on serotonin type 3 receptor.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.215-216
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• 1995

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.585-595
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• 2018

Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 ($5-HT_3$) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with $5-HT_3$ receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the $5-HT_3$ receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. To elucidate the mechanism of amitriptyline, we simulated the $5-HT_3$ receptor currents using Berkeley $Madonna^{(R)}$ software and calculated the rate constants of the agonist binding and receptor transition steps. The $5-HT_3$ receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the $5-HT_3$ receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the $5-HT_3$ receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a $5-HT_3$ receptor, a potential target of neurologic and psychiatric diseases through this study.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.188-195
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• 1993

In order to understand the machanism of action and regulation of ${\beta}$-adrenergic receptor in terms of molecular level, the purification of receptor protein has a fundamental importance. Moreover, species differences among avian, amphibian and mammalian ${\beta}$-adrenergic receptors make it more important to purify mammalian ${\beta}$-adrenergic receptor. Because ${\beta}$-adrenergic receptor is an integral membrane protein, it must be solubilized from the membrane for the purification. The purpose of the present study was to solubilize and characterize the mammalian $\beta$-adrenergic receptor from guinea pig lung in quantities by more efficient and practical method eventually to purify receptor. Guinea pig lung membrane preparation was solubilized by sequential treatment of buffers containing low and high concentration of digitonin which are 0.2 and 1.2% respectively. About 50% of the total receptor pool was released by this double extraction procedure. The $\beta$-adrenoceptors in the digitonin extract were identified using the ${\beta}$-adrenergic antagonist, (-)-[$^3H$]-dihydroalprenolol ([$^3H$]DHA). The solubilized receptor retained all of the essential characteristics of membrane-bound receptor, namely saturability; stereoselectivity; high affinity to ${\beta}$-adrenergic drugs. For the measurement of soluble receptor activity, Sephadex G-50 chromatography method has been widely used. Inspite of its accuracy and wide acceptance, this technique employed troublesome column work which required long time to assay the activity of receptor. We employed another methods to measure receptor activity. When using 0.5% polyethylenimine pretreated GF/B glass fiber filter, filtration technique could be used to measure soluble receptor activity. This technique enabled us to reduce the total amount of time to assay by a factor of 4 as well as to detect soluble receptor. In the present study, we could establish more efficient and practical solubilization method of mammalian $\beta$-adrenergic receptor. The rapidity and high yield of this solubilization scheme, together with the favorable recovery of the receptor activity, are significant steps toward the ultimate purification of the mammalian $\beta$-adrenergic receptor. The result of this study together with more convenient purification method could provide large amount of purified receptor with ease for various research purposes.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.53-53
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• 1993

In considering the mechanism of action of the calcium antagonists, it is important to realize that there are three distinct receptor types and that the new classification divides these three drugs as members of the dihydropyridine, phenylalkylamines and benzothiazipines, respectively. The World Health Organization as well as the International Union of Pharmacology and Cardiology have adopted this classification. Unlike every other class of drugs, such as the alpha and beta adrenergic blocking agents, diuretics, etc., the calcium antagonists need to be thought of as three distinct drug classes. The reason they share some, but not all of the pharmacological profile is that they all act at specific receptor domains present in one large protein of 165 daltons present in all excitable tissue. This protein along with several other subunits make up what is known as the voltage-dependent calcium channel (the so-called "L"type, L-VDCC). The mechanism of action of the three drugs involve first a specfic binding and then an inhibition of the movement of calcium into the cell Some of these drugs, such as diltiazem, may have other interesting intracellular effects perhaps associated with protection of the mitochondria during ischemic insults. The nature of the receptor is being explored by molecular genetic techniques, and we have recently cloned two of the major subunits; some of the data will be presented.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2819-2822
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• 2013

In this study, antiproliferative effects of the selective estrogen receptor modulator Tamoxifen and the aromatase inhibitor letrozole (Femara) were evaluated and compared using the FM3A cell line, originating from a C3H mouse mammary carcinoma and positive in terms of estrogen receptor (ER) expression. Cell kinetic parameters including labelling index, mitotic index and labelling index were assessed after exposure of the. FM3A cell line to $0.001{\mu}g/ml$ of Tamoxifen and $0.25{\mu}g/ml$ of Femara for 4, 8, 16 and 32 h for all parameters. The results showed that cell growth was inhibited by both agents. There was a significant decrease in labelling index and mitotic index and significant increase in apoptotic index for all experimental groups. The differences between control and all experimental groups were statistically significant (p<0.001) for all applications.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.387-391
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• 2015

Background: Fluorine-18 deoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) and bone scintigraphy (BS) are widely used for the detection of bone involvement. The optimal imaging modality for the detection of bone metastases in hormone receptor positive (+) and negative (-) groups of breast cancer remains ambiguous. Materials and Methods: Sixty-two patients with breast cancer, who had undergone both 18F-FDG-PET/CT and BS, being eventually diagnosed as having bone metastases, were enrolled in this study. Results: 18F-FDG-PET/CT had higher sensitivity and specificity than BS. Our data showed that 18F-FDGPET/CT had a sensitivity of 93.4% and a specificity of 99.4%, whiel for BS they were 84.5%, and 89.6% in the diagnosis of bone metastases. ${\kappa}$ statistics were calculated for 18F-FDGPET/CT and BS. The ${\kappa}$-value was 0.65 between 18F-FDG-PET/CT and BS in all patients. On the other hand, the ${\kappa}$-values were 0.70 in the hormone receptor (+) group, and 0.51 in hormone receptor (-) group. The ${\kappa}$-values suggested excellent agreement between all patient and hormone receptor (+) groups, while the ${\kappa}$-values suggested good agreement in the hormone receptor (-) group. Conclusions: The sensitivity and specificity for 18F-FDG-PET/CT were higher than BS in the screening of metastatic bone lesions in all patients. Similarly 18F-FDG-PET/CT had higher sensitivity and specificity in hormone receptor (+) and (-) groups.

• Molecules and Cells
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• v.26 no.3
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• pp.243-249
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• 2008

Corticotropin releasing factor (CRF) mediates various responses to stress through CRF receptors 1 and 2. CRF receptor 2 has two forms, $2{\alpha}$ and $2{\beta}$ each of which appears to have distinct roles. Here we used dopaminergic neuron-derived MN9D cells to investigate the function of CRF receptor 2 in dopamine neurons. We found that n-butyrate, a histone deacetylase inhibitor, induced MN9D cell differentiation and increased gene expression of all CRF receptors. CRF receptor $2{\beta}$ was minimally expressed in MN9D cells; however, its expression dramatically increased during differentiation. CRF receptor $2{\beta}$ expression levels appeared to correlate with neurite outgrowth, suggesting CRF receptor $2{\beta}$ involvement in neuronal differentiation. To validate this statement, we made a CRF receptor $2{\beta}$-overexpressing $MN9D/CRFR2{\beta}$ stable cell line. This cell line showed robust neurite outgrowth and GAP43 overexpression, together with MEK and ERK activation, suggesting MN9D cell neuronal differentiation. From these results, we conclude that CRF receptor $2{\beta}$ plays an important role in MN9D cell differentiation by activating the MEK/ERK signaling pathway.