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Beta adrenergic receptors

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https://www.readbyqxmd.com/read/28813418/mechanism-of-intracellular-allosteric-%C3%AE-2ar-antagonist-revealed-by-x-ray-crystal-structure
#1
Xiangyu Liu, Seungkirl Ahn, Alem W Kahsai, Kai-Cheng Meng, Naomi R Latorraca, Biswaranjan Pani, A J Venkatakrishnan, Ali Masoudi, William I Weis, Ron O Dror, Xin Chen, Robert J Lefkowitz, Brian K Kobilka
G-protein-coupled receptors (GPCRs) pose challenges for drug discovery efforts because of the high degree of structural homology in the orthosteric pocket, particularly for GPCRs within a single subfamily, such as the nine adrenergic receptors. Allosteric ligands may bind to less-conserved regions of these receptors and therefore are more likely to be selective. Unlike orthosteric ligands, which tonically activate or inhibit signalling, allosteric ligands modulate physiologic responses to hormones and neurotransmitters, and may therefore have fewer adverse effects...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28780421/antihypertensive-drugs
#2
REVIEW
Stéphane Laurent
Successful treatment of hypertension is possible with limited side effects given the availability of multiple antihypertensive drug classes. This review describes the various pharmacological classes of antihypertensive drugs, under two major aspects: their mechanisms of action and side effects. The mechanism of action is analysed through a pharmacological approach, i.e. the molecular receptor targets, the various sites along the arterial system, and the extra-arterial sites of action, in order to better understand in which type of hypertension a given pharmacological class of antihypertensive drug is most indicated...
August 2, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28752049/beta-adrenergic-receptors-are-critical-for-weight-loss-but-not-for-other-metabolic-adaptations-to-the-consumption-of-a-ketogenic-diet-in-male-mice
#3
Nicholas Douris, Bhavna N Desai, Ffolliott M Fisher, Theodore Cisu, Alan J Fowler, Eleen Zarebidaki, Ngoc Ly T Nguyen, Donald A Morgan, Timothy J Bartness, Kamal Rahmouni, Jeffrey S Flier, Eleftheria Maratos-Flier
OBJECTIVE: We have previously shown that the consumption of a low-carbohydrate ketogenic diet (KD) by mice leads to a distinct physiologic state associated with weight loss, increased metabolic rate, and improved insulin sensitivity [1]. Furthermore, we identified fibroblast growth factor 21 (FGF21) as a necessary mediator of the changes, as mice lacking FGF21 fed KD gain rather than lose weight [2]. FGF21 activates the sympathetic nervous system (SNS) [3], which is a key regulator of metabolic rate...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28746336/discovery-of-novel-brain-permeable-and-g-protein-biased-beta-1-adrenergic-receptor-partial-agonists-for-the-treatment-of-neurocognitive-disorders
#4
Bitna Yi, Alam Jahangir, Andrew K Evans, Denise Briggs, Kristine Ravina, Jacqueline Ernest, Amir B Farimani, Wenchao Sun, Jayakumar Rajadas, Michael Green, Evan N Feinberg, Vijay S Pande, Mehrdad Shamloo
The beta-1 adrenergic receptor (ADRB1) is a promising therapeutic target intrinsically involved in the cognitive deficits and pathological features associated with Alzheimer's disease (AD). Evidence indicates that ADRB1 plays an important role in regulating neuroinflammatory processes, and activation of ADRB1 may produce neuroprotective effects in neuroinflammatory diseases. Novel small molecule modulators of ADRB1, engineered to be highly brain permeable and functionally selective for the G protein with partial agonistic activity, could have tremendous value both as pharmacological tools and potential lead molecules for further preclinical development...
2017: PloS One
https://www.readbyqxmd.com/read/28744157/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seven-common-drugs-to-inhibit-epithelial-to-mesenchymal-transition-and-augment-capecitabine-efficacy
#5
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28732063/dopamine-acting-at-d1-like-d2-like-and-%C3%AE-1-adrenergic-receptors-differentially-modulates-theta-and-gamma-oscillatory-activity-in-primary-motor-cortex
#6
Mazhar Özkan, Nicholas W Johnson, Umit S Sehirli, Gavin L Woodhall, Ian M Stanford
The loss of dopamine (DA) in Parkinson's is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology...
2017: PloS One
https://www.readbyqxmd.com/read/28720509/the-neuropeptide-galanin-promotes-an-anti-thrombotic-phenotype-on-endocardial-endothelial-cells-from-heart-failure-patients
#7
Christina Tyrrell, Amanda Toyooka, Faiza Khan, Kent L Thornburg, James O Mudd, Wohaib Hasan
Thromboembolic complications are a significant cause of mortality and re-hospitalization in heart failure (HF) patients. One source of thrombi is the ventricular endocardial surface that becomes increasingly pro-thrombotic as HF progresses. Anticoagulation comes with bleeding risks so identifying therapeutic agents for improving cardiac endothelial health are of critical clinical importance. Endocardial endothelial cells are closely apposed to cardiac sympathetic nerves. In HF, cardiac sympathetic nerves are dysregulated and promote disease progression...
September 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28699713/-potential-role-of-norepinephrine-in-the-immune-dysfunction-associated-with-sepsis
#8
Anna Bauer-Dörries, Sarah De Cupis, Lucas Liaudet
Septic shock may be complicated by a state of immune suppression, with ominous prognosis significance. Although the underlying pathophysiological mechanisms are poorly understood, it is possible that norepinephrine, used to treat circulatory failure during septic shock, plays a significant contributing role. Indeed, besides its hemodynamic effects, norepinephrine exerts multiple immunosuppressive actions, which are primarily mediated by beta-2 adrenergic receptors expressed by immune cells. Furthermore, norepinephrine has the ability to promote the growth of numerous bacteria, and could thereby foster the development of nosocomial infections...
July 12, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28670631/cardiac-directed-expression-of-adenylyl-cyclase-catalytic-domain-reverses-cardiac-dysfunction-caused-by-sustained-beta-adrenergic-receptor-stimulation
#9
Mei Hua Gao, N Chin Lai, Dimosthenis Giamouridis, Young Chul Kim, Zhen Tan, Tracy Guo, Wolfgang H Dillmann, Jorge Suarez, H Kirk Hammond
OBJECTIVE: To test the hypothesis that cardiac-directed expression of the cytoplasmic domains of adenylyl cyclase-6 (AC6) would have beneficial effects on the heart. BACKGROUND: Eliminating the two transmembrane domains of AC6 yields a protein with an intact catalytic domain that is disengaged from membrane-associated β-adrenergic receptor stimulation, but with enhanced propensity for intracellular interactions. METHODS: We constructed a peptide of the C1 and C2 segments of AC6 (C1C2), expressed C1C2 in an adenovirus vector and generated transgenic lines with cardiac-directed C1C2 expression, which underwent sustained isoproterenol (Iso) infusion...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28664928/co-activation-of-metabotropic-glutamate-receptor-3-and-beta-adrenergic-receptors-modulates-cyclic-amp-long-term-potentiation-and-disrupts-memory-reconsolidation
#10
Adam G Walker, Douglas J Sheffler, Andrew S Lewis, Jonathan W Dickerson, Daniel J Foster, Rebecca K Senter, Mark S Moehle, Xiaohui Lv, Branden J Stansley, Zixiu Xiang, Jerri M Rook, Kyle A Emmitte, Craig W Lindsley, P Jeffrey Conn
Activation of β-adrenergic receptors (βARs) enhances both the induction of long-term potentiation (LTP) in hippocampal CA1 pyramidal cells and hippocampal-dependent cognitive function. Interestingly, previous studies reveal that coincident activation of group II metabotropic glutamate (mGlu) receptors with βARs in the hippocampal astrocytes induces a large increase in cyclic-AMP (cAMP) accumulation and release of adenosine. Adenosine then acts on A1 adenosine receptors at neighboring excitatory Schaffer collateral terminals, which could counteract effects of activation of neuronal βARs on excitatory transmission...
June 30, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28641581/thyrotoxic-and-pheochromocytoma-multisystem-crisis-a-case-report
#11
Kodai Suzuki, Takahito Miyake, Hideshi Okada, Fuminori Yamaji, Yuichiro Kitagawa, Tetsuya Fukuta, Ryu Yasuda, Yoshihito Tanaka, Haruka Okamoto, Sho Nachi, Tomoaki Doi, Takahiro Yoshida, Keisuke Kumada, Shozo Yoshida, Hiroaki Ushikoshi, Izumi Toyoda, Shinji Ogura
BACKGROUND: Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. CASE PRESENTATION: A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming...
June 23, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28622599/adrenergic-regulation-of-cytoplasmic-structures-related-to-secretory-processes-in-pig-pinealocytes-an-ultrastructural-quantitative-study
#12
Barbara Przybylska-Gornowicz, Bogdan Lewczuk, Natalia Ziółkowska, Magdalena Prusik
Two structures, considered as secretory in nature, are present in the pinealocytes in of the domestic pig show the presence of two structures, which are considered as secretory in nature - the dense core vesicles (DCV) and the membrane bounded (dense) bodies (MBB). The latter are extremely numerous in pig pinealocytes (they occupy 6-20% of the cytoplasm), and the number of MBB changes under different physiological and experimental conditions. Norepinephrine is the main neurotransmitter that regulates the secretion of pineal melatonin...
June 9, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28590038/effects-of-oestrogen-and-cimicifuga-racemosa-on-the-cardiac-noradrenaline-pathway-of-ovariectomized-rats
#13
Yao Liu, Jing Zhang, Shuya Liu, Wenjuan Wang, Xing Chen, Hai Jiang, Junlei Li, Ke Wang, Wenpei Bai, Haicheng Zhang, Lihua Qin
What is the central question of this study? We investigated the effects of oestrogen and Cimicifuga racemosa on the stellate ganglion, cardiac noradrenaline pathway and Ca(2+) -calmodulin-dependent protein kinase II in ovariectomized rats. What is the main finding and its importance? The right stellate ganglion, but not the left, may be associated with decreased left ventricular noradrenaline content in ovariectomized rats. Oestrogen can reverse all changes caused by ovariectomy. Cimicifuga racemosa did not affect left ventricular noradrenaline, but decreased protein expression of β1 -adrenergic receptor and Ca(2+) -calmodulin-dependent protein kinase II...
June 7, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28572492/beta-1-vs-beta-2-adrenergic-control-of-coronary-blood-flow-during-isometric-handgrip-exercise-in-humans
#14
Stephan R Maman, Alvaro F Vargas, Tariq Ali Ahmad, Amanda J Miller, Zhaohui Gao, Urs A Leuenberger, David N Proctor, Matthew D Muller
During exercise, β-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia is not clear. In this study, we simultaneously measured noninvasive indexes of myocardial oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand [i.e., rate pressure product (RPP) = heart rate × systolic blood pressure) and tested the hypothesis that β1 blockade with esmolol improves coronary exercise hyperemia compared with nonselective β-blockade with propranolol...
August 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28557859/beta-2-adrenergic-receptor-genotype-influences-power-output-in-healthy-subjects
#15
Eli F Kelley, Bruce D Johnson, Eric M Snyder
Kelley, EF, Johnson, BD, and Snyder, EM. Beta-2 adrenergic receptor genotype influences power output in healthy subjects. J Strength Cond Res 31(8): 2053-2059, 2017-The purpose of this study was to determine the effects of ADRB2 genotypes on muscle function (absolute power and relative power) in healthy subjects. We performed genotyping of the ADRB2 (amino acid 16) and high-intensity, steady-state exercise on 77 healthy subjects (AA = 18, AG = 25, GG = 34). There were no differences between genotype groups in age, height, weight, or body mass index (BMI) (age = 28...
August 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28488202/autonomic-control-of-body-temperature-and-blood-pressure-influences-of-female-sex-hormones
#16
REVIEW
Nisha Charkoudian, Emma C J Hart, Jill N Barnes, Michael J Joyner
Female reproductive hormones exert important non-reproductive influences on autonomic regulation of body temperature and blood pressure. Estradiol and progesterone influence thermoregulation both centrally and peripherally, where estradiol tends to promote heat dissipation, and progesterone tends to promote heat conservation and higher body temperatures. Changes in thermoregulation over the course of the menstrual cycle and with hot flashes at menopause are mediated by hormonal influences on neural control of skin blood flow and sweating...
May 9, 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/28486910/clinical-significance-of-the-sympathetic-nervous-system-in-the-development-and-progression-of-pulmonary-arterial-hypertension
#17
Ru-Xia Liu, Qian Luo, Hui Qiao, Juan Yu, Qian-Long Zhang, Peng Wang, Yong-Gang Cao, Chang-Lin Jiang, Li-Hui Qu
Pulmonary arterial hypertension (PAH) is defined as a complex disease of clinically characterized by elevated pulmonary pressure eventually resulting in right heart failure and premature death. To date, PAH still remains a life-threatening disease. Published evidence suggests that patients with PAH present profound sympathetic nervous system abnormalities and sympathetic activity has been shown to be increased. The mechanism of PAH is still complex and poorly understood. <p> Results: Some data have showed that adrenoceptors are involved in the process of the pathology and have different functions in the progression of PAH followed by heart failure...
January 12, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28473530/beta-blocker-drug-use-and-survival-among-patients-with-pancreatic-adenocarcinoma
#18
Ruzan Udumyan, Scott Montgomery, Fang Fang, Henrik Almroth, Unnur Valdimarsdottir, Anders Ekbom, Karin E Smedby, Katja Fall
Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register (n = 2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register...
May 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28473352/mir-21-is-involved-in-norepinephrine-mediated-rat-granulosa-cell-apoptosis-by-targeting-smad7
#19
Li Zhang, Jie Gao, Sheng Cui
Substantive evidence has indicated that the sympathetic innervation contributes to the regulation and development of ovarian functions. Norepinephrine (NE) is one of the major neurotransmitters contained in the extrinsic ovarian sympathetic nerves and is thought to be a potent moderator of ovarian functions such as steroidogenesis and granulosa cell proliferation or apoptosis. However, the mechanisms of NE regulation of granulosa cell apoptosis in the rat ovary are rare. Real-time PCR and Western blot results show that NE regulates the expression of miR-21 in primary granulosa cells in a dose-dependent manner...
May 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28469578/beta-adrenergic-regulation-of-intrapulmonary-arteriovenous-anastomoses-in-intact-rat-and-isolated-rat-lungs
#20
Melissa L Bates, Joseph E Jacobson, Marlowe W Eldridge
Intrapulmonary arteriovenous anastomoses (IPAVA) allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol...
2017: Frontiers in Physiology
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