Dexamethasone-Induced Increase in Lymphocyte β-Adrenergic Receptor Density and cAMP Formation in vivo

Pharmacology ◽  
2002 ◽  
Vol 67 (1) ◽  
pp. 1-5 ◽  
Author(s):  
G. Abraham ◽  
G.F. Schusser ◽  
F.R. Ungemach
Keyword(s):  
Adrenergic Receptor ◽  
Receptor Density ◽  
Camp Formation

Response of C-6 glioma to isoproterenol and papaverine in vivo depends on ?-adrenergic receptor density

1984 ◽  
Vol 15 (1) ◽  
pp. 96-99 ◽  
Author(s):  
Ewa Chelmicka-Schorr ◽  
Michael G. Sportiello ◽  
Samir F. Atweh ◽  
Barry G. W. Arnason
Keyword(s):  
Adrenergic Receptor ◽  
Receptor Density

scholarly journals Dynamics of GRK2 in the kidney: a putative mechanism for sepsis-associated kidney injury

2021 ◽  
Author(s):  
Thiele Osvaldt Rosales ◽  
Verônica Vargas Horewicz ◽  
Marcella Amorim Ferreira ◽  
Geisson Marcos Nardi ◽  
Jamil Assreuy
Keyword(s):  
Adrenergic Receptor ◽  
Vascular Reactivity ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Systemic Circulation ◽  
Receptor Density ◽  
No Donor ◽  
In Vivo Experiments ◽  
Renal Vascular

Renal vascular reactivity to vasoconstrictors is preserved in sepsis in opposition to what happens in the systemic circulation. We studied whether this distinct behavior was related to α1 adrenergic receptor density, G protein-coupled receptor kinase 2 (GRK2) and the putative role of nitric oxide (NO). Sepsis was induced in female mice by cecal ligation and puncture (CLP). Wild-type mice were treated with prazosin 12 hours after CLP or NOS-2 inhibitor, 30 min before and 6 and 12 hours after CLP. In vivo experiments and biochemistry assays were performed 24 hours after CLP. Sepsis decreased the systemic mean arterial pressure and the vascular reactivity to phenylephrine. Sepsis also reduced basal renal blood flow which was normalized by treatment with prazosin. Sepsis led to a substantial decreased in GRK2 level associated to an increase in α1 adrenergic receptor density in the kidney. The disappearance of renal GRK2 was prevented in NOS-2-KO mice or mice treated with 1400W. Treatment of non-septic mice with a NO donor reduced GRK2 content in the kidney. Therefore, our results show that a NO-dependent reduction in GRK2 level in the kidney leads to the maintenance of a normal α1 adrenergic receptor density, probably. The preservation of the density and/or functionality of this receptor in the kidney together with a higher vasoconstrictor tonus in sepsis lead to vasoconstriction. Thus, the increased concentration of vasoconstrictor mediators together with the preservation (and even increase) of the response to them may help to explain sepsis-induced acute kidney injury.

scholarly journals Kisspeptin level in the aging ovary is regulated by the sympathetic nervous system

2017 ◽  
Vol 232 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Daniela Fernandois ◽  
Gonzalo Cruz ◽  
Eun Kyung Na ◽  
Hernán E Lara ◽  
Alfonso H Paredes
Keyword(s):  
Adrenergic Receptor ◽  
Follicular Development ◽  
Sympathetic Nerves ◽  
Female Rats ◽  
Reproductive Aging ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Primordial Follicles ◽  
Follicular Cyst

Previous work has demonstrated that the increase in the activity of sympathetic nerves, which occurs during the subfertility period in female rats, causes an increase in follicular cyst development and impairs follicular development. In addition, the increase in ovarian sympathetic activity of aged rats correlates with an increased expression of kisspeptin (KISS1) in the ovary. This increase in KISS1 could participate in the decrease in follicular development that occurs during the subfertility period. We aimed to determine whether the blockade of ovarian sympathetic tone prevents the increase in KISS1 expression during reproductive aging and improves follicular development. We performed 2 experiments in rats: (1) an in vivo blockade of beta-adrenergic receptor with propranolol (5.0 mg/kg) and (2) an ovarian surgical denervation to modulate the sympathetic system at these ages. We measured Kisspeptin and follicle-stimulating hormone receptor (FSHR) mRNA and protein levels by qRT-PCR and western blot and counted primordial, primary and secondary follicles at 8, 10 and 12 months of age. The results showed that ovarian KISS1 decreased but FSHR increased after both propranolol administration and the surgical denervation in rats of 8, 10 and 12 months of age. An increase in FSHR was related to an increase in the number of smaller secondary follicles and a decreased number of primordial follicles at 8, 10 and 12 months of age. These results suggest that intraovarian KISS1 is regulated by sympathetic nerves via a beta-adrenergic receptor and participates locally in ovarian follicular development in reproductive aging.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

Molecular β-adrenergic signaling abnormalities in failing rabbit hearts after infarction

1999 ◽  
Vol 276 (6) ◽  
pp. H1853-H1860 ◽  
Author(s):  
John P. Maurice ◽  
Ashish S. Shah ◽  
Alan P. Kypson ◽  
Jonathan A. Hata ◽  
David C. White ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Ventricular Myocytes ◽  
Myocardial Dysfunction ◽  
Rabbit Model ◽  
Laboratory Model ◽  
Circumflex Coronary Artery ◽  
Biochemical Characteristics ◽  
Protein Levels ◽  
Global Reduction

We studied alterations in the β-adrenergic receptor (β-AR) system of rabbit hearts during the development of heart failure (HF) after myocardial infarction (MI) to determine whether the molecular β-AR abnormalities associated with human HF exist in this animal model. Rabbit HF was established 3 wk after left circumflex coronary artery (LCX) ligation by in vivo physiological measurements, and molecular β-AR signaling was examined in tissue and cultured ventricular myocytes. We found that there was a significant global reduction in β-AR density by ∼50% in both ventricles of MI animals compared with sham-operated control animals and that functional β-AR coupling was significantly reduced. Importantly, as found in human HF, myocardial protein levels and activity of the β-AR kinase (β-ARK1) and Gαi were found to be significantly elevated in MI rabbits, suggesting that these molecules are contributing to myocardial dysfunction. Thus the myocardial β-AR system of this rabbit model of HF shares important biochemical characteristics with human HF and therefore is an ideal laboratory model to investigate novel therapeutic targets for the treatment of HF.

Left ventricular function and beta-adrenoceptors in rabbit failing heart

1990 ◽  
Vol 258 (3) ◽  
pp. H634-H641 ◽  
Author(s):  
N. Gilson ◽  
N. el Houda Bouanani ◽  
A. Corsin ◽  
B. Crozatier
Keyword(s):  
Adrenergic Receptor ◽  
Volume Overload ◽  
Conscious State ◽  
Left Ventricular ◽  
Lv Function ◽  
Receptor Density ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Beta Adrenoceptors ◽  
Chronotropic Response

Few models of heart failure (HF) are available for physiological and pharmacological studies. We report here a model of pressure plus volume overload induced in rabbits in which left ventricular (LV) function was studied in the conscious state after instrumentation of the animals with LV pressure catheter and ultrasonic crystals measuring LV diameter. Beta-Adrenoceptors were studied on crude membranes obtained from control (C) and HF rabbits using [3H]CGP 12177. LV weights and end-diastolic diameters were significantly increased in the HF group compared with the C group (by 79 and 38%, respectively). The percentage of diameter systolic shortening was decreased, in the control state, in rabbits with HF (15.3 +/- 1.6%) as compared with C rabbits (29.6 +/- 2.5%) and remained lower in the HF group when end-systolic pressures were matched. Chronotropic response to isoproterenol injection was significantly decreased in rabbits with HF compared with that of C rabbits. Beta-Adrenergic receptor density was decreased in rabbits with HF (39.3 +/- 3.7 fmol/mg) compared with C rabbits (56.7 +/- 4.2 fmol/mg) without affinity changes. This model of chronic HF thus produces a marked hypertrophy with ventricular dilatation and a depression of LV function within 2 mo, factors that are associated with a reduced cardiac responsiveness to catecholamines and a decreased ventricular beta-adrenergic receptor density.

Increased alpha 1-adrenergic vascular sensitivity during development of hypertension in conscious dogs

1993 ◽  
Vol 264 (4) ◽  
pp. H1259-H1268 ◽  
Author(s):  
N. Uemura ◽  
D. E. Vatner ◽  
Y. T. Shen ◽  
J. Wang ◽  
S. F. Vatner
Keyword(s):  
Adrenergic Receptor ◽  
Peripheral Resistance ◽  
Aortic Pressure ◽  
Conscious Dogs ◽  
Aortic Tissue ◽  
Ang Ii ◽  
Receptor Density ◽  
Adrenergic Stimulation ◽  
Before And After ◽  
Vascular Responsiveness

The goal of this study was to determine whether enhanced vascular responsiveness during the development of perinephritic hypertension is selective or nonspecific. The effects of graded infusions of norepinephrine (NE), phenylephrine (PE), angiotensin II (ANG II), and vasopressin (VP) were examined on mean arterial pressure, total peripheral resistance (TPR), and aortic pressure-diameter relationships in conscious dogs. NE increased TPR significantly greater (P < 0.01) in hypertension than normotension, as did PE infusion, whereas ANG II and VP increased TPR similarly before and after hypertension. Analysis of aortic pressure-diameter relationships also demonstrated significant (P < 0.05) shifts in response to NE and PE, but not ANG II and VP, during the development of hypertension. In normotensive dogs, low doses of ANG II infusion also enhanced the vasoconstrictor response not only to NE and PE but also to VP. In contrast to what was observed in hypertension, in the presence of ANG II infusion after ganglionic blockade, enhanced responses to PE and NE were no longer observed. The alpha 1-adrenergic receptor density in membrane preparations from aortic tissue, as determined by [3H]prazosin binding, was higher (P < 0.05) in hypertensive dogs than control dogs. Thus the vascular responsiveness in the aorta and resistance vessels is enhanced to alpha 1-adrenergic stimulation, but not to all vasoconstrictors, during developing perinephritic hypertension. The mechanism appears to involve increased alpha 1-adrenergic receptor density.

Cellular and functional defects in a mouse model of heart failure

2000 ◽  
Vol 279 (6) ◽  
pp. H3101-H3112 ◽  
Author(s):  
Giovanni Esposito ◽  
L. F. Santana ◽  
Keith Dilly ◽  
Jader Dos Santos Cruz ◽  
Lan Mao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adrenergic Receptor ◽  
Heart Function ◽  
Imaging Techniques ◽  
Single Cells ◽  
Structural Protein ◽  
Muscle Lim Protein ◽  
Intracellular Ca ◽  
Whole Heart

Heart failure and dilated cardiomyopathy develop in mice that lack the muscle LIM protein (MLP) gene (MLP−/−). The character and extent of the heart failure that occurs in MLP−/− mice were investigated using echocardiography and in vivo pressure-volume (P-V) loop measurements. P-V loop data were obtained with a new method for mice (sonomicrometry) using two pairs of orthogonal piezoelectric crystals implanted in the endocardial wall. Sonomicrometry revealed right-shifted P-V loops in MLP−/−mice, depressed systolic contractility, and additional evidence of heart failure. Cellular changes in MLP−/− mice were examined in isolated single cells using patch-clamp and confocal Ca2+ concentration ([Ca2+]) imaging techniques. This cellular investigation revealed unchanged Ca2+ currents and Ca2+ spark characteristics but decreased intracellular [Ca2+] transients and contractile responses and a defect in excitation-contraction coupling. Normal cellular and whole heart function was restored in MLP−/− mice that express a cardiac-targeted transgene, which blocks the function of β-adrenergic receptor (β-AR) kinase-1 (βARK1). These data suggest that, despite the persistent stimulus to develop heart failure in MLP−/− mice (i.e., loss of the structural protein MLP), downregulation and desensitization of the β-ARs may play a pivotal role in the pathogenesis. Furthermore, this work suggests that the inhibition of βARK1 action may prove an effective therapy for heart failure.

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