• Molecules and Cells
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• v.38 no.2
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• pp.105-111
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• 2015

The beta2-adrenergic receptor (${\beta}2AR$) belongs to the G protein coupled receptor (GPCR) family, which is the largest family of cell surface receptors in humans. Extra attention has been focused on the human GPCRs because they have been studied as important protein targets for pharmaceutical drug development. In fact, approximately 40% of marketed drugs directly work on GPCRs. GPCRs respond to various extracellular stimuli, such as sensory signals, neurotransmitters, chemokines, and hormones, to induce structural changes at the cytoplasmic surface, activating downstream signaling pathways, primarily through interactions with heterotrimeric G proteins or through G-protein independent pathways, such as arrestin. Most GPCRs, except for rhodhopsin, which contains covalently linked 11 cis-retinal, bind to diffusible ligands, having various conformational states between inactive and active structures. The first human GPCR structure was determined using an inverse agonist bound ${\beta}2AR$ in 2007 and since then, more than 20 distinct GPCR structures have been solved. However, most GPCR structures were solved as inactive forms, and an agonist bound fully active structure is still hard to obtain. In a structural point of view, ${\beta}2AR$ is relatively well studied since its fully active structure as a complex with G protein as well as several inactive structures are available. The structural comparison of inactive and active states gives an important clue in understanding the activation mechanism of ${\beta}2AR$. In this review, structural features of inactive and active states of ${\beta}2AR$, the interaction of ${\beta}2AR$ with heterotrimeric G protein, and the comparison with ${\beta}1AR$ will be discussed.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1470-1477
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• 2019

${\beta}_2$-adrenergic receptor (${\beta}_2-AR$) was expressed efficiently using Bac-to-Bac Baculovirus Expression System in Sf9 cells as a bio-recognition element for multianalyte screening of ${\beta}$-agonist residues in pork. Sf9 cells were selected as the expression system, and codon optimization of wild-type nucleic acid sequence and time-dependent screening of expression conditions were then carried out for enhancing expression level and biological activity. Under optimum conditions of multiplicity of infection (MOI) = 5 and 48 h post transfection, the protein yield was up to 1.23 mg/ml. After purification by chromatographic techniques, the purified recombinant protein was applied to develop a direct competitive enzyme-linked receptor assay (ELRA) and the efficiency and reliability of the assay was determined. The IC50 values of clenbuterol, salbutamol, and ractopamine were 28.36, 50.70, and $59.57{\mu}g/l$, and clenbuterol showed 47.61% and 55.94% cross-reactivities with ractopamine and salbutamol, respectively. The limit of detection (LOD) was $3.2{\mu}g/l$ and the relevant recoveries in pork samples were in the range of 73.0-91.2%, 69.4-84.6%, and 63.7-80.2%, respectively. The results showed that it had better performance compared with other present nonradioactive receptorbased assays, indicating that the genetically modified ${\beta}_2-AR$ would have great application potential in detection of ${\beta}$-agonist residues.

• Korean Journal of Veterinary Research
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• v.33 no.4
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• pp.617-622
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• 1993

The preliminary studies on the localization of adrenoceptors were performed on smooth muscle strips of bovine esophageal groove. The mechanical activity of the muscle strip was recorded isometrically in vitro.w In the bottom circular muscle strips. the excitatory ${\alpha}-adrenergic$ responses were not blocked by tetrodotoxin$(2.1{\times}10^{-6}M)$ and denervation which was carried by cold storage of strips for 48 hrs in Tyrode's solution at $5-6{^{\circ}C}$ without oxygen supply. These excitatory ${\alpha}-adrenergic$ responses were partially blocked by atropine. In the lip longitudinal muscle strips, the inhibitory${\beta}-adrenergic$ responses were not blocked by pretreatment of tetrodotoxin and atropine. The results suggest that ${\beta}-adrenergic$ receptors mediating relaxations are located on the postsynaptic smooth muscle cells, whereas ${\beta}-adrenergic$ receptors mediating contractions are located both in the smooth muscle cells and in the cholinergic neurones.

• The Korean Journal of Pharmacology
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• v.13 no.1 s.21
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• pp.13-21
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• 1977

The author confirmed the development of the smooth muscle in the oviduct proprius and anterior mesosalpinx in the leghorn, and observed that there was a variation between the action of norepinephrine on albumin-secreting portion of productive oviduct and that of non-productive one, and that $PGE_1$ might play a significant role on the activation of adrenergic ${\alpha}$-receptor in the non-productive oviduct. 1. There were many bundles of smooth muscles with irregular directions, which were identified in the both oviduct proprius and anterior mesosalpinx by Mallory aniline-blue orange G stain. 2. In vitro experiments, the anterior mesosalpinx was always relaxed by norepinephrine. While the albumin-secreting portion of non-productive period of oviduct was relaxed, but that of the productive one contracted by norepinephrine. Both the anterior mesosalpinx and oviduct proprius of chick responsed with relaxation to norepinephrine as shown in the non-productive hen. In vivo experiments, norepinephrine injected through the jugular vein increased the intraoviductal pressure in the productive oviduct, but decreased that in the non-productive one. 3. By treatment with $PGE_1$, in vitro, the relaxation induced not only by norepinephrine, but by periarterial electrical stimulation was converted into contraction, and in the presence of phentolamine, this conversion by $PGE_1$ was not shown. 4. The intra-oviductal pressure of the productive hen treated with indomethacin for 4 days was decreased by norepinephrine, but the increase in pressure by $PGE_1$ or $PGE_{2{\alpha}}$ was supersensitized when these drugs were administered through jugular vein. However, in vivo, the relaxation by norepinephrine was not converted into the stimulation after $PGE_1$ treatment. It might be summarized that the regulation of intra-oviductal pressure was dependent on the summation of the movement of both oviduct and mesosalpinx and intramurally produced prostaglandins contributes to the inherent tone of the prcductive oviduct by activating adrenergic ${\alpha}$-receptor.

• The Korean Journal of Physiology
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• v.7 no.2
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• pp.59-66
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• 1973

It has been reported that vasopressin disperse the melanophore granule of frog skin. The author used hypophysectomized and adrenergic receptor blockaded animals in order to define the mechanism of vasopressin on the melanopore pigment of frog skin. The Rana niglomaculata which could be found in the Seoul area were used on this experiment. The amount of the following drugs were injected into the lymphatic sac of the frog; vaospressin $(0.05\;{\mu}g/g\;B.W.)$, dibenzylin $(0.05\;{\mu}g/g\;B.W.)$, and propranolol $(0.01\;{\mu}g/g\;B.W.)$. The following results were observed; 1. Vasopressin dispersed the melanin granules of melanocyte of frog skin. 2. The melanin granule dispersion activity of vasopressin was observed on the hypophysectomized frog. 3. The melanin granule dispersion was observed on the adrenergic receptor blockaded frog with dibenzylin or propranolol respectively, especially the later one was found to be more obvious. 4. The melanin granule dispersion was observed on the frog which was injected with vasopressin after alpha-receptor or beta-receptor blockade and the later one was found to be more obvious. 5. The melanin granule dispersion was more effective with the blockade of beta-receptor after the treatment with vasopressin on hypophysectomized frog.

• Environmental Mutagens and Carcinogens
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• v.22 no.1
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• pp.39-46
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• 2002

Obesity is a complex metabolic disorder with a strong genetic component. There are many candidate genes for obesity and its related phenotypes. We studied genetic variations between Korean obese and lean groups. Polymorphisms investigated were the Msp I polymorphism of the $\alpha$$_{2A}$-adrenergic receptor ($\alpha$$_{2A}$-AR) gene, the Mnl I polymorphism of the $\alpha$$_2$-adrenergic receptor ($\alpha$$_2$-AR) gene, the BstO I polymorphism of the $\beta$$_3$-adrenergic receptor ($\beta$$_3$-AR) gene, the Pml I polymorphism of the lamin A/C (LMNA) gene, the Hga I polymorphism of the clearance receptor (NPRC) gene, the Msp I polymorphism of the leptin gene, BclI polymorphism of the uncoupling protein 1 (UCPI) gene and the Hha I polymorphism of the fatty acid binding protein 2 (FABP2) gene. Among these genetic markers, Pml I polymorphism at the LMNA gene and Bcl I polymorphism at the UCP1 gene were significantly associated with obesity. However, further studies are required whether thease findings are reproduced in large population, although two polymorphisms might be useful as genetic markers in the ethiology of obesity in Korean population.ion.

• Journal of Radiation Industry
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• v.10 no.4
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• pp.181-187
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• 2016

Selective ${\beta}_1$-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective ${\beta}_1$-antagonists including nebivolol have high binding affinity on ${\beta}_1$-adrenergic receptor, not ${\beta}_2$-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective ${\beta}_1$-blockers in clinically used ${\beta}_1$-blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective ${\beta}_1$-blocker. Nebivolol is $C_2$-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of $^{18}F$. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for $^{18}F$-aromatic substitution, was synthesized in moderate yield which was readily subjected to $^{18}F$-aromatic substitution to give $^{18}F$-labelled nebivolol.

• The Korean Journal of Pharmacology
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• v.8 no.1
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• pp.41-47
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• 1972

The author studied the adrenotropic receptors of isolated vas deferens from Ditrema temmincki Bleeker, using adrenergic activators such as epinephrine, norepinephrine, isoproterenol and phenylephrine, and adrenergic blocking agents such as phenoxybenzamine and propranolol. The results are as follows: 1. The vas deferens was stimulated by epinephrine, norepinephrine and phenylephrine, but not affected by isoproterenol. 2. The excitatory effect of phenylephrine on the vas deferens was completely blocked by phenoxybenzamine, but more stimulated by propranolol. 3. The excitatory effects of epinephrine and norepinephrine were markedly reduced by phenoxybenzamine, but stimulated by propranolol. 4. The vas deferens pretreated with phenoxybenzamine and propranolol was not affected by epinephrine and norepinephrine. 5. The vas deferens was not affected by isoproterenol and also not affected by the pretreatment with either kind of blocking agent plus isoproterenol. 6. It seemed that the vas deferens had both alpha-excitatory receptor and beta-receptor, but it was difficult to detect the character of beta-receptor whether it was inhibitory or excitatory.

• Korean Journal of Plant Resources
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• v.23 no.6
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• pp.513-518
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• 2010

In the present study, the antinociceptive profiles of Dianthus chinensis L extract were examined in ICR mice. Dianthus chinensis L extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Dianthus chinensis L 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 Dianthus chinensis L extract. Intraperitoneal (i.p.) pretreatment with yohimbine ($\alpha_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Dianthus chinensis L extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Dianthus chinensis L extract in the writhing test. Our results suggest that Dianthus chinensis L extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Dianthus chinensis L extract may be mediated by $\alpha_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• Korean Journal of Veterinary Service
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• v.19 no.2
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• pp.154-162
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• 1996

The effcets of adenosine 5'-triphosphate(ATP) were investigated on the uterine smooth muscle motility in the pig. The results were summarized as follows: 1. The effects of the porcine uterine smooth muscle and the contractile responses increased between the concentration of ATP $10^{-5}$ and $10^{-3}$ M with a dose-dependent manner. 2. The contractile response induced by ATP($10^{-4}$ M) was not blocked by pretreatment with cholinergic receptor blocker, atropine ($10^{-6}$ M) 3. The contractile response induced by ATP ($10^{-4}$ M) was not blocked by pretreatment with $\alpha$ -adrenergic receptor blocker, phentolamine(10$^{-6}$ M) and ${\beta}$-adrenergic blocker, propranolol ($10^{-6}$ M). 4. The contractile response induced by ATP($10^{-4}$ M) was not appeared in 4Ca^{++}$ -free medium. As the concentration of $Ca^{++}$ in $Ca^{++}$ -free medium was increased, the contractile response induced by ATP ($10^{-4}$ M) was enhenced but was completely inhibited by pretreatment with $Ca^{++}$ -channel blocker, papaverine($10^{-6}$ M) or verapamil($10^{-6}$ M). From these results, it was conclued that the effects of ATP were the contraction mediated by purinergic receptor in uterine smooth muscle of pig.