• 한국영양학회:학술대회논문집
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• 한국영양학회 2002년도 춘계학술대회
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• pp.100-100
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• 2002

• Journal of Microbiology and Biotechnology
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• 제29권9호
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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.

• 방사선산업학회지
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• 제10권4호
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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.

• Journal of Korean Biological Nursing Science
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• 제10권1호
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• pp.80-87
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• 2008

Purpose: Hypoestrogenism caused by ovariectomy, disease, or menopause is associated with increased obesity in women. Altered fat distribution and weight gain are consequences of menopausal hypoestrogenism, but the mechanisms responsible are not completely known. This study examined the effect of estrogen on obesity in ovariectomized rats. Method: The groups of female rats were 4 weeks post ovariectomy (OVX) or, 4 weeks post-sham operation (SHAM), and 2 weeks post ovariectomy followed by 2 weeks replacement with estradiol benzoate (ER-$16{\mu}g$/kg, subq, qd). Serum ghrelin level was measured by radioimmunoassay (RIA). The expression of adrenergic receptors in adipose tissue was measured by Western blotting assay. Result: OVX significantly increased body weight, serum cholesterol. Two weeks estrogen replacement reduced body weight accompanied by the increment of serum ghrelin and the reduction of the receptor ratio of adrenergic ${\alpha}_{2A}/{\beta}_1$, and ${\alpha}_{2A}/{\beta}_3$. Conclusion: We provide evidence that estrogen reduces obesity through the altered receptor ratio of adrenergic ${\alpha}_{2A}/{\beta}_1$, and ${\alpha}_{2A}/{\beta}_3$ in adipose tissue in ovariectomized rats.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.295-295
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• 1994

The human ${\beta}$$_2$-adrenergic receptor (h${\beta}$$_2$AR) contains seven clusters of hydrophobic amino acids suggestive of membrane-spanning domains and its gene is intronless. The genomic gene encoding h${\beta}$$_2$AR has been isolated by polymerase chain reaction. To express h${\beta}$$_2$AR in Saccharomyces cerevisiae, a modified h${\beta}$$_2$AR gene was fused to signal peptide sequence of Killer toxin gene from Kluyveromyces lactics. This fusion gene was expressed under the galactose-inducible GAL10 promoter. The ligand binding experiments showed that the functional h${\beta}$$_2$AR was expressed at a concentration three times as much as that found in Hamster lung.

• Toxicological Research
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• 제18권3호
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• pp.233-240
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• 2002

In view of the effect of $\beta_2$-Adrenergic receptors ($\beta_2$-AR) as a risk factor for essential hypertension, we investigated the Fnu4HI and MnlI RFLPs of $\beta_2$ -AR gene in the Korean patients with essential hypertension and normal controls. There were no significant differences in the allele and genotype of these polymorphisms between normotensive and essential hypertensive subjects. In ethnic comparison, the allele frequencies of these three sites contained Nde I RFLP reported the association with essential hypertension in Korean population previously, were very different from those of other ethnic populations studied. The significant linkage disequilibrium was detected only in hypertensive group between Nde I and Fnu4HI sites. The Fnu4HI RFLP was also significantly associated with plasma triglyceride (TG) level. Therefore, our results suggest that the significant association between Fnu4HI variation in the human $\beta_2$-AR gene and plasma TG level may reflect the potential role of human $\beta_2$-AR gene as one of the genetic components for cardiovascular risk.

• 대한약리학회지
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• 제31권2호
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• pp.219-231
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• 1995

Vasoactive intestinal polypeptide(VIP) and ${\beta}-adrenergic$ agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a ${\beta}-adrenergic$ receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to ${\beta}-adrenergic$ receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.

• International Journal of Oral Biology
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• 제38권3호
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• pp.121-126
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• 2013

Tumor necrosis factor alpha ($TNF{\alpha}$) is a multifunctional inflammatory cytokine that regulates various cellular and biological processes. Increased levels of $TNF{\alpha}$ have been implicated in a number of human diseases including diabetes and arthritis. Sympathetic nervous system stimulation via the beta2-adrenergic receptor (${\beta}2AR$) in osteoblasts suppresses osteogenic activity. We previously reported that $TNF{\alpha}$ upregulates ${\beta}2AR$ expression in murine osteoblastic cells and that this modulation is associated with $TNF{\alpha}$ inhibition of osteoblast differentiation. In our present study, we explored whether $TNF{\alpha}$ induces ${\beta}2AR$ expression in human osteoblasts and then identified the downstream signaling pathway. Our results indicated that ${\beta}2AR$ expression was increased in Saos-2 and C2C12 cells by $TNF{\alpha}$ treatment, and that this increase was blocked by the inhibition of NF-${\kappa}B$ activation. Chromatin immunoprecipitation and luciferase reporter assay results indicated that NF-${\kappa}B$ directly binds to its cognate elements on the ${\beta}2AR$ promoter and thereby stimulates ${\beta}2AR$ expression. These findings suggest that the activation of $TNF{\alpha}$ signaling in osteoblastic cells leads to an upregulation of ${\beta}2AR$ and also that $TNF{\alpha}$ induces ${\beta}2AR$ expression in an NF-${\kappa}B$-dependent manner.

• 대한약리학회지
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• 제13권2호
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• pp.49-59
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• 1977

Adrenergic receptors are now classified into alpha type and beta type These adrenergic receptors are distributed in various tissue in different patterns. Therefore, the adrenergic response of a certain tissue may be different from those of the other tissues, and such differences may exist among various species of animals. In this paper, the authors attempt to reevaluate the effect of epinephrine on the isolated atria, aortic strips, and vas deferenses of rabbits preincubated with alpha receptor blockades (ergotamine and dibenamine) and beta receptor blockades (propranolol and dichloroisoproterenol) in Locke-Ringer bathing medium. The results obtained were summarized as follows; 1) The dose dependent responses of isolated atria to epinephrine were significantly inhibited by propranolol and dichloroisoproterenol, and slightly inhibited by dibenamine, but not affected by ergotamine. 2) The dose dependent responses of excised aortic strips to epinephrine were significantly inhibited by ergotamine and dibenamine, but the responses were slightly potentiated by propranolol, and significantly by dichloroisoproterenol. 3) The dose dependent responses of isolated vas deferenses to epinephrine were significantly inhibited by ergotamine and dibenamine, but slightly potentiated by propranolol and dichloroisoproterenol.

• BMB Reports
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• 제55권4호
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• pp.187-191
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• 2022

Obesity is caused by an imbalance between energy intake and energy expenditure. Exercise is attracting attention as one of the ways to treat obesity. Exercise induces 'beige adipogenesis' in white adipose tissue, increasing total energy expenditure via energy dissipation in the form of heat. Also, beige adipogenesis can be induced by treatment with a beta-adrenergic receptor agonist. We developed a Cidea-dual reporter mouse (Cidea-P2A-Luc2-T2A-tdTomato, Luciferase/tdTomato) model to trace and measure beige adipogenesis in vivo. As a result, both exercise and injection of beta-adrenergic receptor agonist induced beige adipogenesis and was detected through fluorescence and luminescence. We confirmed that exercise and beta-adrenergic receptor agonist induce beige adipogenesis in Cidea-dual reporter mouse, which will be widely used for detecting beige adipogenesis in vivo.