• The Korean Journal of Pharmacology
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• v.13 no.2
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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.

• The Korean Journal of Pharmacology
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• v.3 no.1
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• pp.43-49
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• 1967

Supplemental studies were made on the adrenotropic receptors of the rat uterus, using adrenergic activators such as phenylephrine, norepinephrine, epinephrine, and isoproterenol and adrenergic blocking agents such as phenoxybenzamine and inderal. The studies have revealed the following results : 1. Phenylephrine, norepinephrine, epinephrine, and isoproterenol inhibited the spontaneous motility of the isolated rat uterus in the following order : Isoproterenol>epinephrine>norepinephrine>phenylephrine. 2. The inhibitory responses of the isolated rat uterus to phenylephrine and epinephrine were abolished by the pretreatment with phenoxybenzamine. 3. The inhibitory responses of the isolated rat uterus to isoproterenol and epinephrine were not affected by phenoxybenzamine. 4. The motility of the isolated rat uterus pretreated with inderal was stimulated by phenylephrine, norepinephrine and epinephrine. 5. The inhibitory responses of the isolated rat uterus to isoproterenol were abolished by the pretreatment with inderal. 6. The motility of the isolated rat uterus pretreated with inderal and phenoxybenzamine was not affected by phenylephrine, norepinephrine and epinephrine. 7. It is, therefore, concluded that the rat uterus has both alpha excitatory and beta inhibitory receptors, with beta inhibitory receptors predominating.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2953-2957
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• 2016

Background: Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked ${\beta}2-adrenergic$ receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. Materials and Methods: We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel-Haenszel, Student t, and ANOVA tests were performed for data analysis. Results: On average, patients were $54.8{\pm}11.8$ years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for ${\beta}1$ - and ${\beta}2$ -adrenergic-receptors did not present metastasis globally, but patients treated with ${\beta}1$ BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. Conclusions: In Mexican patients with BCa and SAH treated with non-selective (${\beta}1$- and ${\beta}2-adrenergic$ receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

• 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.

• Korean Journal of Veterinary Research
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• v.33 no.1
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• pp.71-80
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• 1993

The central nervous system depressant effect of xylazine and xylazine-ketamine was studied in chicken and mice. Intraperitoneal injection of xylazine(1~30 mg/kg) and xylazine(1~30 mg/kg)-ketamine(100 mg/kg) induced a loss of the righting reflex in chicken and mice, respectively. These effects of xylazine were dose-dependent. The results obtained were as follows; 1. The effect of xylazine-induced depression was antagonized by adrenergic antagonists having ${\alpha}_2$-blocking activity(yohimbine, tolazoline, piperoxan and phentolamine). 2. Yohimbine was most effective in the reduction of the CNS depression by xylazine. 3. Phenoxybenzamine and prazosin did not reduced CNS depression by xylazine in both species. 4. Labetalol (${\alpha}_1$, ${\beta}_1$-adrenergic antagonist) and propranolol(${\beta}$-adrenergic blocking agent) were not effective in reducing xylazine induced depression. 5. Cholinergic blocking agents (atropine and mecamylamine), a dopaminergic antagonist (Haloperidol), a histamine $H_1$-antagonist(chlorpheniramine), a histamine $H_2$-antagonist(cimetidine), a serotonergic-histamine $H_1$ antagonist(cyproheptadine) were not effective in reducing xylazine-induced depression. 6. Xylazine-induced depression is mediated by ${\alpha}_2$-adrenergic receptors and appears not to be involved in cholinergic, dopaminergic, serotonergic or histaminergic pathways.

• The Korean Journal of Pharmacology
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• v.16 no.1 s.26
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• pp.9-14
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• 1980

To evaluate the adrenergic receptors for glycogenolytic responses to catecholamine, the blood glucose level, liver glycogen content and muscle glycogen level in rats were studied with treatment of epinephrine, norepinephrine and isoproterenol. In addition, to study the possibility of interconversion of adrenergic receptors, the effects of catecholamines in feeding animal were compared with those in fasting animal. The results are summarized as follow; 1) Epinephrine and norepinephine showed dose dependent increase of blood glucose level but the effect of isproterenol was not significant. 2) The prandial states of animal did not influence on effects of catecholamines on blood glucose level. 3) Liver glycogen contents were lowered by epinephrine or by norepinephrins but effect of isoproterenol was not significant. 4) Glycogen content of skeletal muscle was significantly lowered by isoproterenol and. epinephrine shifted the dose-response curve to right, but the effect of norepinephrine was not significant. 5) The effects of epinephrine and norepinephrine on blood glucose were significantly blocked by ergotamine but not by propranolol. These results indicate that the glycogenolytic response to adrenergic agents in rat is mediated by an alpha-receptor in liver and by a beta-receptor in skeletal muscle.

• Biomolecules & Therapeutics
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• v.2 no.4
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• pp.303-309
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• 1994

The analysis of membrane receptors for hormones and neurotransmitters has progressed considerably by pharmacological and biochemical means and more recently through the use of specific antibodies. Two kinds of antibodies could be produced, one is from synthetic peptides and the other from proteins such as purified receptor. Anti-peptide antibodies gave some advantages; epitope is evident and also receptor purification in quantity is not prerequisite. It can be also applied to the study of receptor structure-activity relationship. The purpose of the present study was 1) to produce and characterize a polyclonal antibody against a synthetic $\beta$2-adrenergic receptor peptide(Phe-Gly-Asn-Phe-Trp-Cys-Phe-Trp-Thr-Ser-Ile-Asp-Val-Leu) and 2) to determine the effects of this antibody on the $\beta$-adrenergic receptor ligand interaction. The peptide sequence contains an amino acid residue such as Asp-113 which was identified as one of important component for receptor-ligand interaction in site-directed mutagenesis studies. Production of antibody was performed by immunization of rabbits through popliteal lymph node with the peptide coupled with Keyhole Limpet Hemocyanin (KLH). The titer of antibody against this peptide was 1 : 1000. The anti-peptide antibody was able to detect a 67 kDa protein band in western blot corresponding to the molecular weight of the $\beta$-adrenergic receptor in partially purified receptor fraction derived from guinea pig lung. The antisera inhibited the specific binding of [$^3$H]dihydroalprenolol to $\beta$-adrenergic receptor in a concentration-dependent manner. The results from this study suggest that the peptide sequence selected in the present study is important for the receptor ligand interaction.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.86-86
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• 1995

The analysis of membrane receptors for hormones and neurotransmitters has progressed considerably by pharmacological and biochemical means and more recently by the use of specific anti-receptor antibodies. A 14-mer peptide (from Phe102 to Leu115 of ${\beta}$2-adrenergic receptor) was synthesized and this peptide was coupled to carrier protein Keyhole Limpet Hemocyanin(KLH) by glutaraldehyde method. A 0.5mg of KLH-coupled peptide was emulsified with equal volume of complete Freund's adjuvant and injected via popliteal lymph node to each of the three Newzealnd White rabbits. Booster injections were repeated at 4 weeks interval for three times with incomplete Freund's adjuvants. One week after the final injection, serum was prepared from ear artery. Nonspecific immunoglobulins were removed by passing the serum through KLH-Sepharose 6B affinity matrix and further by incubation with bovine lung aceton powder. The titer of the antibody for synthetic peptide which was determined by enzyme linked immunosorbent assay(ELISA) was about l/l,000. The antibody produced in this study revealed 67kDa protein band in the western blot of partially purified guinea pig lung ${\beta}$-adrenergic receptor preparation. The antibody inhibited ${\beta}$-adrenergic antaginist [3H] Dihydroalprenolol binding to soluble ${\beta}$-adrenergic receptor by 25% while control sera did not show any inhibitory effects, The result of this study suggests that the peptide sequence selected in this study may play some important roles in adrenergic receptor-ligand interaction.

• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.580-587
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• 2005

New evidence is emerging that airway smooth muscle(ASM) may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, polypeptide growth factors, extracellular matrix proteins, cell adhesion receptors and co-stimulatory molecules. ASM can promote the formation of the interstitial extracellular matrix, and potentially contribute to the alterations within the extracellular matrix in asthma. In addition, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells through integrin-directed signaling. Increased ASM mass is one of the most important features of the airway wall remodeling process in asthma. Three different mechanisms may contribute to the increased ASM mass : cell proliferation, increased migration and decreased rate of apoptosis. The major signaling pathways of cell proliferation activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. The key signaling mechanisms of cell migration have been identified as the p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways. ASM cells contain ${\beta}2$-adrenergic receptors and glucocorticoid receptors. They may represent a key target for ${\beta}2$-adrenergic receptor agonist/corticosteroid interactions which have antiproliferative activity against a broad spectrum of mitogens.

• Toxicological Research
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• v.18 no.3
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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.