Nonspecific Effects of Ligands on the β-Adrenergic Receptors in Rabbit Abdominal Aorta in vitro

2013 ◽  
Vol 61 (3) ◽  
pp. 263-269
Author(s):  
Jan Gnus ◽  
Albert Czerski ◽  
Jolanta Bujok ◽  
Stanisław Ferenc ◽  
Wojciech Zawadzki ◽  
...  
Keyword(s):  
Abdominal Aorta ◽  
Adrenergic Receptors ◽  
Nonspecific Effects ◽  
Β Adrenergic Receptors

β-Adrenergic receptors, voltage-operated Ca 2+-channels, nuclear triiodothyronine receptors and triiodothyronine concentration in pig myocardium after long-term low-dose amiodarone treatment

1993 ◽  
Vol 129 (4) ◽  
pp. 337-347 ◽  
Author(s):  
Liv Bjørn-Hansen Gøtzsche
Keyword(s):  
Cardiac Surgery ◽  
Nuclear Receptors ◽  
Adrenergic Receptors ◽  
Low Dose ◽  
Binding Capacity ◽  
Drug Concentrations ◽  
Cardiac Strain ◽  
Amiodarone Treatment ◽  
Β Adrenergic Receptors

Similar features during chronic amiodarone treatment and hypothyroidism suggest that amiodarone induces a state of "triiodothyronine (T3)-resistance" or "cardiac hypothyroidism", which may predispose the heart to pump failure under conditions with severe strain, such as recovery after cardiac surgery. Disagreements exist as to how amiodarone, and possibly its main metabolite desethylamiodarone, act upon the various receptor systems in the heart. The aim of the present study was to elucidate whether chronic amiodarone treatment leads to a functional reduction in the number of myocardial nuclear T3 receptors, the myocardial tissue T3 concentration and the number of β-receptors and voltage-operated Ca2+-channels. Finally, special attention was drawn to any changes that could contribute to explain previous reports on reduced haemodynamic reserve in animals exposed to severe cardiac strain, such as cardiac surgery. Pigs (72±2 kg) were assigned randomly to amiodarone treatment (20 mg·kg−1·day−1 for 30±1 days, N = 8); controls received no medical treatment (N = 6). The left ventricle was evaluated for β-adrenergic receptors, voltage-operated Ca2+-channels, T3 nuclear receptors and tissue T3 concentration. Maximum binding capacity for β-receptors and Ca2+-channels was reduced in amiodarone-treated pigs (by 38%, p<0.05, and by 52%, p<0.01) and correlated with tissue drug concentrations for both receptor types (p<0.05). No changes were observed concerning nuclear T3 receptors. In vitro competition studies revealed that amiodarone, but not desethylamiodarone, possessed binding properties to Ca2+-channels, whereas neither of the compounds bound to β-receptors. Desethylamiodarone, but not amiodarone, competitively inhibited T3 binding to its nuclear receptors. Myocardial T3 was undetectable (<0.05 nmol/kg wet wt) in amiodarone-treated pigs. From our observations we suggest that the active metabolite desethylamiodarone, rather than the parent drug, is mainly responsible for the observed local hypothyroid-like effects during amiodarone treatment. The observed changes after treatment with low-dose amiodarone in pigs are likely to have biological implications. Functionally, the changes may imply reduced cardiac reserve during conditions of extraordinary strain.

scholarly journals Sympathetic nerve activity promotes cardiomyocyte cell-cycle arrest and binucleation

2017 ◽  
Author(s):  
Li Chen ◽  
Alexander Y. Payumo ◽  
Kentaro Hirose ◽  
Rachel B. Bigley ◽  
Jonathan Lovas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Sympathetic Nerve ◽  
Adrenergic Receptors ◽  
Sympathetic Nerve Activity ◽  
Cardiomyocyte Proliferation ◽  
Nerve Activity ◽  
Cycle Arrest ◽  
Β Adrenergic Receptors

ABSTRACTAdult mammalian hearts typically have little capacity to regenerate after injuries such as myocardial infarction. In contrast, neonatal mice during the first week of life possess an incredible ability to regenerate their hearts, though this capacity is lost shortly after birth. The physiological triggers mediating this transition remains poorly understood. In this study, we demonstrate that sympathetic nerve activity promotes cardiomyocyte cell-cycle arrest and binucleation. In mice hearts lacking sympathetic nerve inputs, we observe increased mononucleated cardiomyocyte numbers and elevated cardiomyocyte proliferation. Additionally, increased cardiomyocyte mononucleation and proliferation are observed in mice with genetic and pharmacological inhibition of β-adrenergic receptors (βARs), which mediate sympathetic nerve signaling. Using in vitro cultures of neonatal cardiomyocytes, we demonstrate that activation of β-adrenergic receptors results in decreased cardiomyocyte proliferation that is mediated through cyclic AMP-dependent protein kinase (PKA) signaling. Taken together, these results suggest that sympathetic nerve activity may play a role in limiting the ability of mammalian hearts to regenerate by restricting cardiomyocyte proliferation and promoting cytokinesis failure leading to multinucleation.

Demonstration of β-adrenergic receptors in rat nasal glands by an in vitro autoradiographic technique

1988 ◽  
Vol 90 (1-2) ◽  
pp. 75-77 ◽  
Author(s):  
Y.J.B. van Megen ◽  
C.J.B.M. van Ratingen ◽  
A.B.M. Klaassen ◽  
J.F. Rodrigues de Miranda ◽  
C.A.M. van Ginneken ◽  
...  
Keyword(s):  
Adrenergic Receptors ◽  
Autoradiographic Technique ◽  
Β Adrenergic Receptors ◽  
Nasal Glands

Interaction between prolactin and catecholamines on hypothalamic GnRH release in vitro

1996 ◽  
Vol 151 (2) ◽  
pp. 269-275 ◽  
Author(s):  
A E Calogero ◽  
N Burrello ◽  
A M Ossino ◽  
R F A Weber ◽  
R D'Agata
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Experimental Conditions ◽  
Adrenergic Mechanism ◽  
Gnrh Release ◽  
Β Adrenergic Receptors

Abstract Brain catecholamines have been implicated in the regulation of gonadotrophin release. It has been recently reported that noradrenaline (NA), applied within the hypothalamic paraventricular nucleus, suppresses the pulsatile release of LH in the rat through a corticotrophin-releasing hormone (CRH)-dependent mechanism. Prolactin (PRL) is also able to suppress hypothalamic GnRH release following activation of the CRH-releasing neurone. Given that PRL stimulates the release of NA from hypothalamic explants and that NA stimulates the release of hypothalamic CRH, we hypothesized that this neurotransmitter may be involved in the intrahypothalamic neuroendocrine circuit mediating the inhibitory effects of PRL on GnRH release. To test this hypothesis, we evaluated the effects of PRL on GnRH release in the presence of α- or β-adrenergic receptor antagonists using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated, longitudinally halved hypothalami. As previously shown, PRL at a concentration of 100 nm inhibited basal iGnRH release by about 35%. Phentolamine, a non-selective α-adrenergic receptor antagonist, prazosin, an α1-receptor antagonist, and yohimbine, an α2-receptor antagonist, overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. In contrast, propranolol, a non-selective β-adrenergic receptor antagonist, atenolol, a β1-receptor antagonist, and ICI-118,551, a β2-receptor antagonist, had no effect. None of these compounds had any effect on basal iGnRH release. These findings suggested that an α-adrenergic mechanism is involved in the suppressive effects of PRL on GnRH release. Since the activation of α-adrenergic receptors increases hypothalamic CRH release, we evaluated whether PRL stimulates CRH release via an α-adrenergic mechanism. PRL stimulated basal CRH release by about twofold and this effect was inhibited by phentolamine in a concentration-dependent fashion. In conclusion, α-, but not β-, adrenergic receptors mediate the inhibitory effects of PRL on GnRH release in vitro. We speculate that, at least under these experimental conditions, PRL inhibits GnRH release through an α-adrenergic mechanism which activates the CRH-secreting neurone. Journal of Endocrinology (1996) 151, 269–275

MECHANISM OF OESTRADIOL ACTION ON THE RAT UTERUS: INDEPENDENCE OF CYCLIC AMP, PROSTAGLANDIN E2 AND β-ADRENERGIC MEDIATION

1973 ◽  
Vol 58 (3) ◽  
pp. 525-533 ◽  
Author(s):  
U. ZOR ◽  
Y. KOCH ◽  
S. A. LAMPRECHT ◽  
J. AUSHER ◽  
H. R. LINDNER
Keyword(s):  
Cyclic Amp ◽  
Adrenergic Receptors ◽  
Tissue Concentration ◽  
Ovariectomized Rats ◽  
Minor Role ◽  
Prostaglandin E ◽  
Rat Uterus ◽  
Stimulatory Action ◽  
Β Adrenergic Receptors

SUMMARY The hypothesis that cyclic AMP plays an essential role in mediating the biological action of oestradiol on the uterus, was tested by determining the tissue concentration of the cyclic nucleotide after incubation of uteri of immature rats with oestradiol or after injection of this steroid into immature or ovariectomized rats. The effect of known stimulants of uterine adenyl cyclase, namely β-adrenergic drugs and prostaglandin E2 (PGE2), on the level of cyclic AMP in the uterus was also examined both in vitro and in vivo. In either system, oestradiol failed to enhance the concentration of cyclic AMP in the uterine tissue, whereas adrenaline or the almost purely β-adrenergic agonist isoprenaline (isoproterenol) caused cyclic AMP accumulation that was susceptible to inhibition by the β-adrenergic blocking agent propranolol. Prostaglandin E2, and to a much lesser degree prostaglandin F2α, increased cyclic AMP concentration in the uterus, but the effect of PGE2 was not inhibited by propranolol. It may be concluded that oestradiol does not cause appreciable stimulation of PGE2 synthesis or activation of β-adrenergic receptors in the rat uterus since, otherwise, increased cyclic AMP production should have been observed after the treatment with oestradiol. Isoprenaline mimicked the stimulatory action of oestradiol on uterine ornithine decarboxylase. However, this action of isoprenaline was abolished by propranolol, whereas that of oestradiol was only slightly, though significantly, inhibited. The present findings do not support the view that the action of oestradiol on the uterus is mediated by cyclic AMP, and also suggest that β-adrenergic receptors and PGE2 can have only a minor role, if any, in the mechanism of action of this hormone.

scholarly journals Control of cytokinesis by β-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment

2019 ◽  
Vol 11 (513) ◽  
pp. eaaw6419 ◽  
Author(s):  
Honghai Liu ◽  
Cheng-Hai Zhang ◽  
Niyatie Ammanamanchi ◽  
Sangita Suresh ◽  
Christopher Lewarchik ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adrenergic Receptors ◽  
Transcriptional Profiling ◽  
Pulmonary Stenosis ◽  
Underlying Mechanism ◽  
The United States ◽  
Heart Tissue ◽  
Developing Heart ◽  
Β Adrenergic Receptors

One million patients with congenital heart disease (CHD) live in the United States. They have a lifelong risk of developing heart failure. Current concepts do not sufficiently address mechanisms of heart failure development specifically for these patients. Here, analysis of heart tissue from an infant with tetralogy of Fallot with pulmonary stenosis (ToF/PS) labeled with isotope-tagged thymidine demonstrated that cardiomyocyte cytokinesis failure is increased in this common form of CHD. We used single-cell transcriptional profiling to discover that the underlying mechanism of cytokinesis failure is repression of the cytokinesis gene ECT2, downstream of β-adrenergic receptors (β-ARs). Inactivation of the β-AR genes and administration of the β-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. Propranolol enabled the division of ToF/PS cardiomyocytes in vitro. These results suggest that β-blockers could be evaluated for increasing cardiomyocyte division in patients with ToF/PS and other types of CHD.

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