• Title/Summary/Keyword: ${\beta}_2$-adrenergic Receptor

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Different effects of prolonged β-adrenergic stimulation on heart and cerebral artery

  • Shin, Eunji;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin;Kim, Nari
    • Integrative Medicine Research
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    • v.3 no.4
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    • pp.204-210
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    • 2014
  • The aim of this review was to understand the effects of ${\beta}$-adrenergic stimulation on oxidative stress, structural remodeling, and functional alterations in the heart and cerebral artery. Diverse stimuli activate the sympathetic nervous system, leading to increased levels of catecholamines. Long-term overstimulation of the ${\beta}$-adrenergic receptor (${\beta}AR$) in response to catecholamines causes cardiovascular diseases, including cardiac hypertrophy, stroke, coronary artery disease, and heartfailure. Although catecholamines have identical sites of action in the heart and cerebral artery, the structural and functional modifications differentially activate intracellular signaling cascades. ${\beta}AR$-stimulation can increase oxidative stress in the heart and cerebral artery, but has also been shown to induce different cytoskeletal and functional modifications by modulating various components of the ${\beta}AR$ signal transduction pathways. Stimulation of ${\beta}AR$ leads to cardiac dysfunction due to an overload of intracellular $Ca^{2+}$ in cardiomyocytes. However, this stimulation induces vascular dysfunction through disruption of actin cytoskeleton in vascular smooth muscle cells. Many studies have shown that excessive concentrations of catecholamines during stressful conditions can produce coronary spasms or arrhythmias by inducing $Ca^{2+}$-handling abnormalities and impairing energy production in mitochondria, In this article, we highlight the different fates caused by excessive oxidative stress and disruptions in the cytoskeletal proteome network in the heart and the cerebral artery in responsed to prolonged ${\beta}AR$-stimulation.

Effects of Cardiovascularly Acting Neuroendocrine Agents on Heart Beatings of Pacific Oyster, Crassostrea gigas (순환기 기능 조절기능을 가진 신경내분비계 작용물질이 참굴의 심장 수축기능에 미치는 영향)

  • Park, Kwan-Ha
    • The Korean Journal of Malacology
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    • v.25 no.1
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    • pp.15-22
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    • 2009
  • Because it is known that bivalve hearts contain various modulatory systems activated by neuroendocrine substances, it was examined whether different classes of endogenous and synthetic drugs of neuroendocrinological importance can influence cardiac functions of the Pacific oyster Crassostrea gigas. Cholinergically active agents acetylcholine and carbachol increased heart rates while diminishing cardiac contractility. Adrenergically active substances norepinephrine (NE) and epinephrine (Epi) also induced heart rate increase and contractility decrease. An $\alpha_1$-adrenergic receptor-selective agonist phenyephrine (PE) failed to modulate either parameter. The Epi-induced heart rate increase and contractile depression were both blocked significantly by non-selective $\beta_1/\beta_2$-adrenergic antagonist propranolol. A $\beta_1$-selective antagonist atenolol prevented Epi-induced heart rate decrease but not the contractile depression, suggesting possible $\beta_2$ receptors for Epi-induced contractile depression. The three autacoids examined exerted discrete responses: histamine increased heart rate and depressed contraction; $\gamma$-amino-butyric acid increased both parameters; serotonin failed to change either parameter. The 5 piscine anesthetic agents examined, MS-222, benzocaine, quinaldine, urethane, pantocaine and pentobarbital, all failed to influence the cardiac function of oysters. Collectively, activities of neuroendocrinologically acting agents in mammals showed unexpected and distinct activities from those in mammalian cardiovascular systems. These results obtained from substances of different physiological functions can serve as a basis for understanding neuroendocrine control of the heart function in Pacific oyster.

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Study of Gene-gene Interaction within GNB3, ACE, ADRB3, ADRB2 among Korean Female Subject (한국인 비만 여성의 GNB3, ACE, ADRB3, ADRB2 유전자 다형성간의 상호관계에 관한 연구)

  • Choi Hyun;Bae Hyun su;Hong Moo chang;Shin Hyun Dae;Shin Min Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.5
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    • pp.1426-1436
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    • 2004
  • There have been several reports on the relationship between G protein β3 subunit gene (GNB3), angiotensin converting enzyme gene (ACE), β3-adrenergic receptor gene (ADRB3), and β2-adrenergic receptor gene (ADRB2) genotype and obesity or obesity related disease. The objective of this study was to examine the relationship between the combinations of these four genes' polymorphism and probability of obesity related disease in Korean female subjects. The experimental group was consisted of 85 obese Korean female subjects (body mass index, BMI≥27㎏/㎡). To determine the polymorphism, genomic DNA was isolated, and PCR was performed. Serological examinations (fasting plasma glucose, FPG; aspartate aminotranferase, AST; alanine aminotransferase, ALT; total cholesterol, TC; triglyceride, TG; high density lipoprotein-cholesterol, HDL; low density lipoprotein-choles terol, LDL) were carried by an autoanalyzer and serological methods. BMI, waist circumference (WC), hip circumference and waist hip ratio (WHR) were measured. Consequencely in the analysis with grouping of general genotyping and variant allele carrier/non-carrier, the result was not significantly different within all gene combinations and polymorphic pairings except higher waist circumference in Arg16Arg group of ADRB2 codon16 (P=0.024). And there was no significantly contrast result about age, height, weight, AST and ALT that are index feature of liver and gall bladder disease in polymorphic pairings of gene combinations. However, the statistical analysis of waist-hip ratio and waist circumference that could be recognized as the physical type of obesity showed T-Arg16 pairing carrier in GNB3-ADRB2 codon16 combination had increased WHR and WC significantly (P=0.046 and P=0.015 respectively). Futhermore, the levels of total cholesterol (TC) and low density lipoprotein choresteral (LDL) were significantly lower in C-I pairing of GNB3-ACE combination (P=0.032 and P=0.005). These results suggest that the T-Arg16 pairing carrier in GNB3-ADRB2 codon16 gene might have increased waist circumference and C-I pairing carrier in GNB3-ACE combination have lower possibility of contraction of cardiovascular disease related cholesterol and LDL despite of obese state.

Comparative Analysis of Obesity by $\beta$-II, III, Adrenergic Receptor Gene Polymorphism in Korean Young Females ($\beta$-II, III Adrenergic Receptor 유전자 다형성에 따른 20대 한국여성의 식이 섭취량, 비만도 및 체성분의 비교연구)

  • 홍정미;김중학;박윤신;최선미;윤유식;안홍석
    • Journal of Nutrition and Health
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    • v.35 no.8
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    • pp.870-879
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    • 2002
  • The purpose of this study was to investigate the obesity and state of dietary intake of 216 young Korean females, and the influence of $\beta$-II, III Adrenergic receptor (AR) gene polymorphism upon obesity and dietary intake. The average weight, height and BMI of the subjects were 160 cm, 54 kg, and 20.9 kg/$m^2$, respectively. The average triceps skinfold thickness, waist circumference, hip circumference and WHR were 21.7mm, 73.1cm, 93.3cm and 0.78, respectively. The results of body composition measurement using bioimpedance method, average body fluid, body protein, mineral mass and body fat were 29.271, 7.22 kg, 6.79 kg and 19.16 kg, respectively. A dietary survey was conducted using 24-hour recall method. Average calorie intake was 1621 ㎉, which is 81% of Korean RDA. We detected 182 (84.3%) Gln27 (QQ) homozygotes and 34 (15.7%) Gln27Glu (QE) heterozygotes for $\beta$-II AR polymorphism. For $\beta$-III AR polymorphism, we detected 163 (75.5%) Trp64 (WW) and 53 (24.5%) Trp 64Arg (WR). The results of comparing of obesity by $\beta$-II AR gene polymorphism, obesity index and BMI of QE type were slightly higher than those of the QQ type. For $\beta$-III AR gene polymorphism, the mean BMI, obesity index, fat mass and percent body fat (%) of the WR type were significantly higher than those of the WW type (p < 0.05). These findings suggest that genetic variability in the human $\beta$-III AR is associated with obesity among young Korean females. We also evaluated the effect of the simultaneous presence of the $\beta$-II AR and $\beta$-III AR polymorphism on obesity. We found that the BMI and obesity index of the mutant type in both $\beta$-II AR and $\beta$-III AR were significantly higher than those of the type that has only one gene mutation or has no mutation (p < 0.05), indicating a synergistic effect of $\beta$-II AR and $\beta$-III AR polymorphism on obesity. No association was found between $\beta$-II Ad or $\beta$-III AR polymorphism and dietary intake.

Effect of imipramine or ECS on central $\beta_1$and $\beta_2$receptor Sensitivity in the Cardiovascular Response of Rat

  • Sohn, Uy-Dong;Kim, Choong-Young;Huh, In-Hoi
    • Archives of Pharmacal Research
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    • v.12 no.4
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    • pp.282-288
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    • 1989
  • This study was investigated the effects of imipramine (IMI) and electroconvulsive shock (ECS), which are used as antidepressant therapy, on the central $\beta_1$or $\beta_2$ adrenergic receptor in anesthetized rats. The resting blood pressure and heart rate decreased in reserpinized group (5 mg/kg i. p., 24 hr before), but not in order 4 groups i. e. acute IMI (20 mg/kg i. p.. 3-5 hr before), chronic IMI (Same dose, twice a day for 14 days), siggle ECS (sinusoidal 20 Hz, 120 V for 2 sec) and repeated ECS (same condition, daily for 12 days). The increase of heart rate and hypotension evoked by 1 or 3 $\mu$g intracerebroventricular (i. c. v.) administration of (+) dobutamine, $\beta_2$-agonist, 1 or 3 $\mu$g i. c. v. was significantly attenuated in repeated ECS or reserpine treatment. And, the diminuation of pulse pressure of salbutamol also reduced by repeated ECS. These results suggest that IMI or ECS result in attenuation on tachycardia by (+) dobutamine or on hypotension by salbutamol, presumably by which the central $\beta_1$ or $\beta_2$receptor sensitivity may be suppressed, repectively.

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Effects of the $\beta$3-Adrenergic Receptor Genotype on Hyperglycemic Risk Among Korean Women

  • Oh, Hyun-Hee;Kim, Kil-Soo;Park, Sun-Mi;Yang, Hyun-Sung;Yoosik Yoon
    • Nutritional Sciences
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    • v.6 no.4
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    • pp.239-245
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    • 2003
  • The $\beta$3-adrenergic receptor ($\beta$3AR) plays a major role in thermogenesis and lipolysis in brown and visceral adipose tissue, and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of $\beta$3AR gene polymorphism on the risk of hyperglycemia in 980 Korean women who attended a weight loss program in a local clinic. Each subject s height, weight, BMI, WHR, obesity index and body composition were measured. The genotype of the $\beta$3AR gene in codon 64 was analyzed by the PCR RFLP method. Serum concentrations of fasting glucose, of total and HDL cholesterol, and of TG were determined. Genotype distributions were as follows : 67% WW type, 31% WR type, and 2% RR type. Among the many measured parameters, fasting glucose levels were significantly higher in the WR/RR type compared with the WW type (p=0.0ll). When the subjects were divided into two groups by a fasting blood glucose level higher or lower than 6.105mmol/L (110mg/dl), the frequency of hyperglycemia showed a significant difference in relation to $\beta$3AR genotype as measured by $\X^2$-analysis (p=0.014); the frequency of hyperglycemia was significantly higher (at 24.8%) in WR/RR type subjects, compared to 18.2% in WW type subjects. When all of the measured parameters were included in stepwise logistic regression analyses to find the risk factors for hyperglycemia, the odds ratios for hyperglycemia were 1.573 (p=0.0ll) for the WR/RR type of the $\beta$3AR gene, 1.053 (p=0.001) for TG, 1.044 (p=0.037) for BMI, and 1.026 for age (p=0.031). These data suggest that the WR/RR genotype of the $\beta$3AR has a very strong association with increased blood glucose level and might be a significant risk factor for hyperglycemia among Korean women.

Mutation Analysis in β2-Adrenergic Receptor Gene by Denaturing High Performance Liquid Chromatography (DHPLC) (DHPLC를 이용한 β2-교감신경수용체 유전자에서의 돌연변이 분석)

  • Park, Sang-Bum;Oh, Chung-Hun;Kim, Jong-Wan;Jang, Won-Cheoul
    • Analytical Science and Technology
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    • v.15 no.3
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    • pp.190-195
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    • 2002
  • We analysed mutation of ${\beta}_2$-adrenergic receptor gene that controls bronchial asthma by denaturing high performance liquid chromatography (DHPLC) according to ion-pair reversed-phase high performance liquid chromatography (IP-RP-HPLC). We extracted genomic DNA from 50 asthma patients, amplified DNA using PCR, and analysed PCR product by DHPLC. As a result, we obtained that mutation frequency was 15 (30%) among 50 cases. Consequently DHPLC mutation detection was confirmed that the result of direct sequencing was coincide exactly.

Metastasis Risk Reduction Related with Beta-Blocker Treatment in Mexican Women with Breast Cancer

  • Parada-Huerta, E;Alvarez-Dominguez, TP;Uribe-Escamilla, R;Rodriguez-Joya, JF;Ponce-Medrano, JA Diaz;Padron-Lucio, S;Alfaro-Rodriguez, A;Bandala, C
    • 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.

Cardiac physiologic regulation of sub-type specific adrenergic receptors in transgenic mice overexpressing β1- and β2-adrenergic receptors.

  • Kim, Ka Eul;Tae, Hyun-Jin;Natalia, Petrashevskaya;Lee, Jae-Chul;Ahn, Ji Hyeon;Park, Joon Ha;Kim, In Hye;Ohk, Taek Geun;Park, Chan Woo;Cho, Jun Hwi;Won, Moo-Ho
    • Clinical and Experimental Emergency Medicine
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    • v.3 no.3
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    • pp.175-180
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    • 2016
  • Objective Combination of ${\beta}_1-adrenergic$ receptor (AR) blockade and ${\beta}_2-AR$ activation might be a potential novel therapy for treating heart failure. However, use of ${\beta}-AR$ agonists and/or antagonists in the clinical setting is controversial because of the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. Methods In this study, we performed hemodynamic evaluation by examining force frequency response (FFR), Frank-Starling relationship, and response to a non-selective ${\beta}-AR$ agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing ${\beta}_1-$ and ${\beta}_2-ARs$ (${\beta}_1-$ and ${\beta}_2-AR$ TG mice, respectively). Results Cardiac physiologic consequences of ${\beta}_1-$ and ${\beta}_2-AR$ overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in ${\beta}_2-AR$ TG mice. ${\beta}_1-AR$ TG mice showed a pronounced negative limb of FFR, whereas ${\beta}_2-AR$ TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both ${\beta}_1-$ and ${\beta}_2-AR$ TG mice. Conclusion Hemodynamic evaluation performed in the present showed a difference in ${\beta}_1-$ and ${\beta}_2-AR$ signaling, which may be due to the difference in the desensitization of ${\beta}_1-$ and ${\beta}_2-ARs$.