• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
• /
• pp.305-305
• /
• 1994

It has been shown that there are several subtypes of $\kappa$ opioid receptor, We have evaluated the properties of non-${\mu}$, non-$\delta$ binding of 〔$^3$H〕DIP, a nonselective opioid antagonist, in rat cortex membranes. Binding to ${\mu}$ and $\delta$ sites was inhibited by the use of an excess of competing selective agonists (DAMGO, DPDPE) for these sites. (-)Ethylketocyclazocine(EKC) inhibited 〔$^3$H〕DIP binding with Ki. of 70 nM. However, arylacetamides (U69593 and U50488H) gave little inhibition. Also, we have examined the opioid modulation of K$\^$+/(30 mM)-induced histamine release in rat frontal cortex slices labeled with 1-〔$^3$H〕histidine. The 〔$^3$H〕histamine release from cortex slices was inhibited by EKC, a $\kappa$$_1$-and $\kappa$$_2$-agonist, in a concentration-dependent manner(10 to 10,000 nM). The IC$\sub$50/ of EKC was 107 ${\pm}$ 6 nM. However, the $\delta$ receptor selective agonists, DPDPE and deltorphine II, ${\mu}$ receptor agonists, DAMGO and TAPS, $\kappa$$_1$-agonists, U69593 and U50488H, and $\varepsilon$-agonist, ${\beta}$-endorphin, did not inhibit histamine release even in micromoiar dose, indicating that ${\mu}$, $\delta$ or $\kappa$$_1$ receptors are not involved. The concentration-response curve of EKC was shifted to right in the presence of naloxone (300 nM), a ${\mu}$ preferential antagonist, norbinaltorphimine(300 nM), a $\kappa$$_1$ preferential antagonist and bremazocine(1 nM), a $\kappa$$_1$-agonist and $\kappa$$_2$-antagonist. These results suggest that $\kappa$$_2$ opioid receptor regulates histamine release in the frontal cortex of the rat.

• Archives of Pharmacal Research
• /
• 제9권4호
• /
• pp.219-222
• /
• 1986

Dose-dependent increasesin blood glucose were produced by epinephrine and clonidine in fasted male mice. Isoproterenol was ineffective in increasing blood glucose at lower doses ($10^{-8}M$/kg-$10^{-7}M$/kg); with higher dose ($10^{-6}M$/kg) the glucose level was increased. The hyperglycemia induced by epinephrine was inhibited by yobimbine, prazosin and propranolol, indicating that the hyperglycemic effect of epinephrine is mediated by alpha-1, alpha-2 and beta adrenoceptor. When clonidine (10$^{-6}$ M/kg) was administered simultaneously with sioproterenol ($10^{-6}M$/kg), an enhenced hyperglycemic effect was observed. The increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These results suggest that stimulation of alpha-2 adrenoceptor may be reponsible for the exertion of the hyperglycemic effect by beta agonists in fasted mice.

• 한국환경농학회지
• /
• 제41권2호
• /
• pp.135-151
• /
• 2022

BACKGROUND: The β-agonists known as phenyl ethanolamine derivatives have a conjugated aromatic ring with amino group. They are used as tocolytic agents and bronchodilator to human and animal generally, and some of them are used as growth promoters to livestock. METHODS AND RESULTS: β-agonists in samples were extracted by 0.4 N perchloric acid and ethyl acetate. The target compounds were analyzed by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). Validation of method was performed according to CODEX guidelines (CAC/GL-71). The matrix matched calibration gave correlation coefficients>0.98, and the obtained recoveries were in the range of 62.0-109.8%, with relative standard deviation ≤ 20.1%. In addition, a survey was performed to inspect any residual β-agonist from 100 samples of livestock and fishery products and ractopamine was detected in one of the 100 samples. CONCLUSION(S): In this study, we established the analytical method for β-agonists through using the expanded target compounds and samples. And we anticipate that the established method would be used for analysis to determine veterinary drug residues in livestock and fishery products.

• Natural Product Sciences
• /
• 제5권1호
• /
• pp.25-32
• /
• 1999

The pharmacological actions of ambrein were investigated alone or in combination as a pretreatment with agonists (adrenaline, noradrenaline, acetylcholine, histamine, nicotine), antagonists (atropine, atenolol) and calcium channel blocker (verapamil) in vivo in anaesthetized SWR rats using blood pressure, heart rate and myocardial contractility as parameters. Ambrein in the dose range of 50-200 mg/kg to the normotensive anaesthetized rats demonstrated negative chronotropic effect and increased the myocardial contractility significantly. At the mid dose (100 mg/kg) this increase in contractile force was 36% and 44% above the normal at 30 min and 60 min intervals post-treatment, respectively. Both of the lower and high doses (50 mg/kg and 200 mg/kg) had similar effects. Furthermore, this contractile response was dose related. Also, this compound produced a considerable increase in myocardial contractility when used as a pretreatment with some agonists and antagonists. The results on blood pressure did not show a considerable change when ambrein was used alone. However, ambrein pretreatment at the dose of 100 mg/kg did not block the effects of adrenaline, noradrenaline, isoprenaline and acetylcholine on heart rate and blood pressure. On the other hand, this pretreatment attenuated the sympathoadrenal effects of nicotine significantly. Chronotropic and blood pressure changes produced by histamine were also inhibited by ambrein pretreatment. This pretreatment significantly reversed the effects of atenolol but failed to demonstrate any change in the negative chronotropic, inotropic and hypotensive responses induced by verapamil. It is concluded that ambrein induced nonselective dose dependent antagonism of the effects of some agonists and antagonists require contribution of some neuromediators. However, the positive isotropic effects of ambrein possibly involve the enhancement of slow Ca channels and/or activation of ${\beta}-adrenergic$ receptors in the heart. At this moment it is difficult to explain the exact mode of action of ambrein and the studies dealing with Ca channel blocker and adrenergic blocker followed by ambrein may help to define the factors which contribute to its positive inotropic effects.

• International Journal of Oral Biology
• /
• 제46권1호
• /
• pp.39-44
• /
• 2021

This study aimed to investigate whether neurotransmitter receptors in the nervous system were also expressed in oral keratinocytes. Expressions of various neurotransmitter receptor genes in immortalized mouse oral keratinocyte (IMOK) cells were examined by reverse transcriptase polymerase chain reaction. IMOK cells expressed calcitonin gene-related peptide (CGRP) receptor subunit genes Ramp1 and Ramp3 and glutamate receptor subunit genes Grina, Gria3, Grin1, Grin2a, and Grin2d. Moreover, IMOK cells expressed Adrb2 and Chrna5 that encode beta 2 adrenergic receptor and cholinergic receptor nicotinic alpha 5 for sympathetic and parasympathetic neurotransmitters, respectively. The expression of Bdkrb1 and Ptger4, which encode receptors for bradykinin and prostaglandin E2 involved in inflammatory responses, was also observed at low levels. Expressions of Ramp1 and Grina in the mouse gingival epithelium were also confirmed by immunohistochemistry. When the function of neurotransmitter receptors expressed on IMOK cells was tested by intracellular calcium response, CGRP, glutamate, and cholinergic receptors did not respond to their agonists, but the bradykinin receptor responded to bradykinin. Collectively, oral keratinocytes express several neurotransmitter receptors, suggesting the potential regulation of oral epithelial homeostasis by the nervous system.

• Membrane and Water Treatment
• /
• 제13권6호
• /
• pp.321-335
• /
• 2022

Copper-based Metal-organic framework (MOF) namely ([Cu (INA)₂]-MOF) is synthesized by ball milling and characterized using scanning electron microscopy (SEM) for the topography, microstructure, and elemental evidence determination, powdered X-ray diffraction (XRD) for the crystallinity measurement, thermogravimetric (TG) analysis was performed to determine the thermal stability of the material, and Fourier transformed infrared (FTIR) spectroscopy for functional groups identification. The use of [Cu (INA)₂]-MOF as hazardous removal material of β-agonists as persistent hazardous micro-pollutants in our environmental water is first reported in this study. The removal efficiency of the Cu-MOF is successfully determined to be 97.7% within 40 minutes, and the MOF has established an exceptional removal capacity of 835 mg L^-1 with 95 % percent removal on Clenbuterol (CLB) even after the 5th consecutive cycle. The Langmuir model of the adsorption isotherms was shown to be more favourable, while the pseudo-second-order model was found to be favoured in the kinetics. The reaction was exothermic and spontaneous from a thermodynamic standpoint, and the higher temperatures were unfavourable for the adsorption study of the CLB. As a result, the studied MOF have shown promising properties as possible adsorbents for the removal of CLB in wastewater.

• Bulletin of the Korean Chemical Society
• /
• 제32권6호
• /
• pp.2008-2014
• /
• 2011

Serotonin or 5-hydroxytryptamine subtype 2C ($5-HT_{2C}$) receptor belongs to class A amine subfamily of G-protein-coupled receptor (GPCR) super family and its ligands has therapeutic promise as anti-depressant and -obesity agents. So far, bovine rhodopsin from class A opsin subfamily was the mostly used X-ray crystal template to model this receptor. Here, we explained homology model using beta 2 adrenergic receptor (${\beta}$2AR), the model was energetically minimized and validated by flexible ligand docking with known agonists and antagonists. In the active site Asp134, Ser138 of transmembrane 3 (TM3), Arg195 of extracellular loop 2 (ECL2) and Tyr358 of TM7 were found as important residues to interact with agonists. In addition to these, V208 of ECL2 and N351 of TM7 was found to interact with antagonists. Several conserved residues including Trp324, Phe327 and Phe328 were also found to contribute hydrophobic interaction. The predicted ligand binding mode is in good agreement with published mutagenesis and homology model data. This new template derived homology model can be useful for further virtual screening based lead identification.

• 약학회지
• /
• 제47권4호
• /
• pp.244-251
• /
• 2003

Asthma is a chronic inflammatory disease of the airway and the prevalence rate is increasing. As the burden of asthma to the society is significant due to the increasing hospital admissions and emergency visits, National Heart, Lung and Blood Institute (NHLBI, USA) and World Health Organization (WHO) have developed comprehensive guidelines to help clinicians and patients make appropriate decisions about asthma care. The aim of study was to analyze the pattern of asthma prescriptions based on the national asthma guidelines for the patients visiting primary health care providers. Prescription data for asthma were obtained from the Korean National Health Insurance claims database of January 2002. Ten percent of the primary health care providers were sampled based on their specialty areas, and 20％ of the claim cases were randomly chosen. Study results showed that prescription rate for oral beta-2 agonists was 44.3％, and that for oral theophylline was 46.9％. Oral steroids were prescribed for the 28.2％ of the claims. Utilization of inhalers was low for both bronchodilators (20.3％, beta-2 agonists inhalers), and steroids (8.4％ steroids inhalers). Bronchodilators were more preferred to the longterm anti-inflammatory controllers among the primary health care providers. Prescription rate for antibiotics was 46.0％ for asthmatic patients. Also gastrointestinal drugs were prescribed for 59.0％, antitussives 65.3％, antihistamines 25.3％ and analgesics 29.4％, respectively. This study presented that the prescribing pattern of the primary health care providers for the asthma was quite different from the national and international guidelines. More efforts need to be made to reduce the gap between the present pattern of asthma prescription and the guidelines.

• Tuberculosis and Respiratory Diseases
• /
• 제82권3호
• /
• pp.190-193
• /
• 2019

Inhaled corticosteroids (ICSs) have been widely used as a key medication for asthma control. However, ICSs have been known to cause respiratory infections, such as pneumonia and pulmonary tuberculosis. Consequently, a dilemma exists regarding recommendation of persistent lifetime use of ICSs to mild asthma patients. Short-acting ${\beta}$-agonists (SABAs) have also been widely used for symptom relief. However, SABAs have been reported to increase the risk of asthma-related death, though incidences have been very rare. Consequently, a dilemma exists regarding recommendation of a SABA alone without an ICS or a controller to asthma patients even with very mild disease. In the real world, asthma patients tend to intermittently use ICS and more likely to be dependent on SABA since many patients want immediate relief of their symptoms. Consequently, a dilemma exists regarding the underuse of ICSs but the overuse of SABAs. One strategy for solving the presented dilemma would be identification of patients with asthma who require persistent use of asthma controllers. Such patients, who may be referred to as "persistent controller users," should continuously receive ICSs, even under controlled states of asthma. Another strategy would be a patient-adjusted, symptom-driven, intermittent-to-regular treatment combining low-dose ICS/rapid-onset long-acting ${\beta}$-agonists instead of using a SABA alone or with low-dose ICS for the asthma patients with mild disease. Both of these two strategies could avoid the risky treatment of a SABA alone without an ICS and could reduce the dose of ICS with the maintenance of asthma control.

• The Korean Journal of Physiology and Pharmacology
• /
• 제11권2호
• /
• pp.37-43
• /
• 2007

Adenosine has been reported to provide cytoprotection in the central nervous systems as well as myocardium by activating cell surface adenosine receptors. However, the exact target and mechanism of its action still remain controversial. The present study was performed to examine whether adenosine has a protective effect against $A{\beta}$-induced injury in neuroglial cells. The astrocyte-derived human neuroglioma cell line, A172 cells, and $A{\beta}_{25{\sim}35}$ were employed to produce an experimental $A{\beta}$-induced glial cell injury model. Adenosine significantly prevented $A{\beta}$-induced apoptotic cell death. Studies using various nucleotide receptor agonists and antagonists suggested that the protection was mediated by $A_1$ receptors. Adenosine attenuated $A{\beta}$-induced impairment in mitochondrial functional integrity as estimated by cellular ATP level and MTT reduction ability. In addition, adenosine prevented $A{\beta}$-induced mitochondrial permeability transition, release of cytochrome c into cytosol and subsequent activation of caspase-9. The protective effect of adenosine disappeared when cells were pretreated with 5-hydroxydecanoate, a selective blocker of the mitochondrial ATP-sensitive $K^+$ channel. In conclusion, therefore we suggest that adenosine exerts protective effect against $A{\beta}$-induced cell death of A172 cells, and that the underlying mechanism of the protection may be attributed to preservation of mitochonarial functional integrity through opening of the mitochondrial ATP-sensitive $K^+$ channels.