Binding of the hydrophilic β-adrenergic antagonist [3H]CGP-12177 to cardiac tissue slices: characterization and ontogenetic studies in dogs

1987 ◽  
Vol 65 (9) ◽  
pp. 1928-1933 ◽  
Author(s):  
C. Haddad ◽  
M. Wilkinson ◽  
L. M. Roeder ◽  
J. T. Tildon ◽  
J. A. Armour
Keyword(s):  
Adrenergic Receptors ◽  
Cardiac Tissue ◽  
Tissue Slices ◽  
Tissue Handling ◽  
Neonatal Life ◽  
Adrenergic Antagonist ◽  
Cgp 12177 ◽  
A New Technique ◽  
The Right ◽  
Β Adrenergic Receptors

A new technique was developed to characterize the binding of a hydrophilic β-adrenergic antagonist, [3H]CGP-12177, to 1-mm thick slices of canine cardiac tissue. This technique was used to quantify the density (Bmax) and the affinity (Kd) of these receptors in the right ventricular conus (RVC) and the left ventricle (LV) at day 1 to 6 weeks of age, and in the adult. Binding was found to be reversible, saturable, stereospecific, of high affinity, and thermolabile. There was an increase in the density of β-adrenergic receptors between day 1 (Bmax = 2.2 ± 0.3 fmol/mg tissue in RVC and 2.9 ± 0.8 fmol/mg tissue in the LV) and 2 weeks of age postnatally, after which it remained constant until 6 weeks of age (Bmax = 7.5 ± 0.4 and 6.8 ± 0.9 fmol/mg tissue in RVC and LV, respectively); however, by 6 weeks of age it had not reached adult levels (10.3 ± 1.0 fmol/mg tissue). The affinity of these receptors did not change between early neonatal life (Kd = 1.3 ± 0.4 nM) and adulthood (Kd = 1.4 ± 0.2 nM). The density of β-adrenergic receptors in the RVC was similar to that in the LV. This new method of quantifying β-adrenergic receptors in cardiac tissue is simple and fast, and requires minimal tissue handling. It proved to be useful in studying the development of cardiac β-adrenergic receptors with age.

α-Adrenergic receptor modulation of the intrathoracic efferent sympathetic nervous system regulating the canine heart

1989 ◽  
Vol 67 (10) ◽  
pp. 1199-1204 ◽  
Author(s):  
J. A. Armour
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Blocking Agent ◽  
Sympathetic Ganglia ◽  
Canine Heart ◽  
Receptor Modulation ◽  
Adrenergic Antagonist ◽  
Cervical Ganglia ◽  
Β Adrenergic Receptors ◽  
Stimulation Of

The augmentation of ventricular inotropism induced by electrical stimulation of acutely decentralized efferent sympathetic preganglionic axons was reduced, but still present, following administraiton of hexamethonium (10 mg/kg i.v.). While hexamethonium continued to be administered, the cardiac augmentations so induced were enhanced significantly following administration of the α-adrenergic receptor blocking agent, phentolamine myselate (1 mg/kg i.v.). Stimulation of the sympathetic efferent postganglionic axons in cardiopulmonary nerves induced cardiac augmentations that were unchanged following administration of these agents singly or together. The cardiac augmentations induced by stimulation of efferent preganglionic sympathetic axons were unchanged when phentolamine was administered alone. The augmentations of cardiac inotropism induced by efferent postganglionic sympathetic axonal stimulation were decreased following local administration of the β-adrenergic antagonist timolol into the ipsilateral stellate and middle cervical ganglia. Thereafter, these augmentations were unchanged following the subsequent intravenous administration of phentolamine. It is concluded that the activation of cardiac neurons in the stellate and middle cervical ganglia by stimulation of efferent preganglionic sympathetic axons can be modified by α-adrenergic receptors and that these effects are dependent upon β-adrenergic receptors, not nicotinic ones, in intrathoracic ganglia.Key words: α-adrenergic inotropism, sympathetic ganglia, hexamethonium, phentolamine.

Mediation of isoproterenol-induced thirst in rats by β2-adrenergic receptors

1978 ◽  
Vol 56 (3) ◽  
pp. 465-470 ◽  
Author(s):  
M. J. Katovich ◽  
M. J. Fregly
Keyword(s):  
Water Intake ◽  
Adrenergic Receptors ◽  
Subcutaneous Administration ◽  
Female Rats ◽  
Acute Administration ◽  
Drinking Response ◽  
Adrenergic Antagonist ◽  
Blocking Activity ◽  
Β Adrenergic Receptors ◽  
Adrenergic Blocking

Isoproterenol-induced thirst in rats has been attributed to the activation of β-adrenergic receptors. Since these receptors can be further differentiated pharmacologically into β1 and β2 types, experiments were performed using several β-adrenergic agonists and antagonists to determine the receptor type initiating the isoproterenol-induced thirst. The β1- and β2-adrenergic antagonist, d,l-propranolol (1 mg/kg, ip), blocked the increase in water intake usually accompanying acute subcutaneous administration of isoproterenol (25 μg/kg) to female rats. Since l-propranolol is known to stabilize membranes and to possess anesthetic-like properties, d-propranolol was also used. This isomer has little β-adrenergic-blocking activity but possesses anesthetic-like activity. Administration of d-propranolol (1 mg/kg, ip) failed to affect the drinking response to acute administration of isoproterenol (25 μg/kg). Practolol (125 mg/kg), a β1-adrenergic antagonist with little anesthetic properties, also had no effect on water intake of isoproterenol-treated rats. Butoxamine, a selective β2-adrenergic antagonist, attenuated the drinking response to isoproterenol. Salbutamol (150 μg/kg), a β2-adrenergic agonist, mimicked the effect of isoproterenol on water intake. These results are consistent with the suggestion that β2-adrenergic receptors mediate the isoproterenol-induced thirst in rats.

scholarly journals Non-co-ordinate development of β-adrenergic receptors and adenylate cyclase in chick heart

1982 ◽  
Vol 204 (3) ◽  
pp. 825-830 ◽  
Author(s):  
R W Alexander ◽  
J B Galper ◽  
E J Neer ◽  
T W Smith
Keyword(s):  
Embryonic Development ◽  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Cardiac Tissue ◽  
Beta Adrenergic Receptors ◽  
In Ovo ◽  
Beta Adrenergic ◽  
Receptor Affinity ◽  
Chick Heart ◽  
Β Adrenergic Receptors

We have studied the properties of beta-adrenergic receptors and of their interaction with adenylate cyclase in the chick myocardium during embryogenesis. Between 4.5 and 7.5 days in ovo the number of receptors determined by (-)-[3H]dihydroalprenolol ([3H]DHA) binding is constant at approx. 0.36 pmol of receptor/mg of protein. By day 9 the density decreases significantly to 0.22 pmol of receptor/mg of protein. At day 12.5-13.5 the number was 0.14-0.18 pmol of receptor/mg of protein. This number did not change further up to day 16. The same results were obtained with guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG) added to the assay mixtures. There was no significant change in receptor affinity for the antagonist [3H]DHA between days 5.5 and 13. Despite the decrease in numbers of beta-adrenergic receptors, there was no change in basal, p[NH]ppG-, isoprenaline- or isoprenaline-plus-p[NH]ppG-stimulated adenylate cyclase activity between days 3 and 12 of development. We conclude that beta-adrenergic receptors and adenylate cyclase are not co-ordinately regulated during early embryonic development of the chick heart. Some of the beta-adrenergic receptors present very early in the ontogeny of cardiac tissue appear not to be coupled to adenylate cyclase since their loss is not reflected in decreased activation of the enzyme.

Chronic prenatal hypoxia sensitizes β-adrenoceptors in the embryonic heart but causes postnatal desensitization

2009 ◽  
Vol 297 (2) ◽  
pp. R258-R264 ◽  
Author(s):  
Isa Lindgren ◽  
Jordi Altimiras
Keyword(s):  
Adrenergic Receptors ◽  
Broiler Chickens ◽  
Cardiac Tissue ◽  
Cardiac Development ◽  
Cardiac Contractility ◽  
Prenatal Hypoxia ◽  
Response Curves ◽  
Cgp 12177 ◽  
Cardiac Enlargement ◽  
Fetal Cardiac Development

Prenatal hypoxia in mammals causes fetal growth restriction and catecholaminergic overstimulation that, in turn, alter signaling pathways associated with adrenergic receptors. β-Adrenoceptors (β-ARs) are essential for fetal cardiac development and regulation of cardiac contractility. We studied the effects of chronic prenatal hypoxia on cardiac β-AR signaling and the incidence of alterations in the juvenile β-AR system due to the embryonic treatment. We measured functional β-AR density (Bmax) through binding with [3H]CGP-12177 and the effect of agonists on β-AR-dependent contractility (pEC50) through concentration-response curves to epinephrine. Eggs from broiler chickens were incubated in normoxia (N, 21% O2) or chronic hypoxia (H, 14% O2). Cardiac tissue from embryos and juveniles was used (15 and 19 day of embryonic development and 14 and 35 days posthatching, E19, E15, P14, and P35, respectively). Relative cardiac enlargement was found in the hypoxic groups at E15, E19, and P14, but not P35. Bmax significantly decreased in E19H. Bmax more than doubled posthatching but decreased from P14 to P35. The sensitivity to epinephrine was lower in E19N compared with E15N, but hypoxia increased the sensitivity to agonist in both E15H and E19H. Despite maintained receptor density, the P35H juvenile displayed a decreased sensitivity to β-AR agonist, something that was not seen in P14H. The postnatal decrease in β-AR sensitivity as an effect of chronic prenatal hypoxia, without a concomitant change in β-AR density, leads us to conclude that the embryonic hypoxic challenge alters the future progression of β-AR signaling and may have important implications for cardiovascular function in the adult.

scholarly journals Determination of the desensitization of β-adrenergic receptors by [3H]CGP-12177

1983 ◽  
Vol 216 (3) ◽  
pp. 669-674 ◽  
Author(s):  
C Hertel ◽  
P Müller ◽  
M Portenier ◽  
M Staehelin
Keyword(s):  
Plasma Membrane ◽  
Adrenergic Receptors ◽  
Sucrose Density Gradient ◽  
C6 Glioma Cells ◽  
Beta Adrenergic Receptors ◽  
Cell Compartment ◽  
Beta Adrenergic ◽  
Cgp 12177 ◽  
Β Adrenergic Receptors

Isoprenaline treatment of C6-glioma cells induced a fast decrease in the number of beta-adrenergic receptors as determined by binding of [3H]CGP-12177, which paralleled the decrease in the hormonally stimulated adenylate cyclase activity. The total number of receptors, as determined by binding of (-)-[3H]dihydroalprenolol, did not decrease. Separation of the beta-adrenergic receptors on a sucrose density gradient showed that the decrease in the number of receptors detectable with CGP-12177 was due to a movement of the receptors from the plasma membrane to a vesicular cell compartment. By using both (-)-[3H]dihydroalprenolol and [3H]CGP-12177 it is thus possible to differentiate between the total number of receptors and those present at the plasma membrane in an unfractionated cell lysate.

β-Adrenergic receptors are involved in histamine-induced secretion of proopiomelanocortin-derived peptides and prolactin in rats

1995 ◽  
Vol 132 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Andreas Kjær ◽  
Ulrich Knigge ◽  
Steen Matzen ◽  
Jørgen Warberg
Keyword(s):  
Adrenergic Receptors ◽  
Receptor Agonist ◽  
Receptor Activation ◽  
Anterior Lobe ◽  
Intermediate Lobe ◽  
Central Administration ◽  
Melanocyte Stimulating Hormone ◽  
Adrenergic Antagonist ◽  
Β Receptor ◽  
Β Adrenergic Receptors

Kjær A, Knigge U, Matzen S, Warberg J. β-Adrenergic receptors are involved in histamine-induced secretion of proopiomelanocortin-derived peptides and prolactin in rats. Eur J Endocrinol 1995;132: 223–8. ISSN 0804–4643 The neurotransmitter histamine (HA) is involved in central regulation of secretion of prolactin (PRL) and the proopiomelanocortin (POMC)-derived peptides adrenocorticotropin (ACTH), β-endorphin (β-END) and α-melanocyte-stimulating hormone (α-MSH). The effect of HA on POMC-derived peptides and PRL release is, at least in part, indirect and may involve activation of catecholaminergic systems. Therefore, we investigated the effect of β-adrenergic receptor blockade on HA or HA agonist-induced release of ACTH, β-END, α-MSH and PRL. Central administration of HA, the H1-receptor agonist 2-thiazolylethylamine (2-TEA) or the H2-receptor agonist 4-methylhistamine (4-MeHA) stimulated the secretion of ACTH, β-END, α-MSH and PRL. Pretreatment with the β-adrenergic antagonist propranolol inhibited secretion of the POMC peptides in response to HA, 2-TEA or 4-MeHA. Propranonol only inhibited the PRL response to HA or 2-TEA, but had no effect on the PRL response to 4-MeHA. Administration of the β-receptor agonist isoproterenol stimulated ACTH, β-END, α-MSH and PRL two to five-fold. This effect was totally blocked by pretreatment with propranolol. We conclude that HA-induced secretion of POMC-derived peptides from the anterior and intermediate lobe of the pituitary gland and of PRL from the anterior lobe is, at least in part, mediated via catecholamines. β-Adrenergic receptors are involved in the mediation of the POMC response to H1- as well as H2-receptor activation, whereas β-receptors are involved only in the mediation of the PRL response to H1-receptor activation. Andreas Kjær, Department of Medical Physiology, Division of Endocrinology and Metabolism, The Panum Institute (Building 12.3), University of Copenhagen, Blegdamsvej 3c, DK-2200 Copenhagen N, Denmark

Characterization of [3H]CGP 12177 Binding to β-Adrenergic Receptors in Intact Eel Hepatocytes

2001 ◽  
Vol 121 (3) ◽  
pp. 223-231 ◽  
Author(s):  
Elena Fabbri ◽  
Corrado Selva ◽  
Thomas W. Moon ◽  
Antonio Capuzzo
Keyword(s):  
Adrenergic Receptors ◽  
Cgp 12177 ◽  
Β Adrenergic Receptors

Adenylate cyclase uncoupled β-adrenergic receptors in salamander proximal tubules

1990 ◽  
Vol 68 (7) ◽  
pp. 863-869 ◽  
Author(s):  
Nikolas S. Morgunov ◽  
David J. Hirsch
Keyword(s):  
Adenylate Cyclase ◽  
Proximal Tubule ◽  
Adrenergic Receptors ◽  
Proximal Tubules ◽  
Ambystoma Tigrinum ◽  
Adenylate Cyclase System ◽  
Binding Studies ◽  
Binding Characteristics ◽  
Cgp 12177 ◽  
Β Adrenergic Receptors

The isolated perfused proximal tubule of the neotenic salamander Ambystoma tigrinum responds with either a hyperpolarization or depolarization of both the basolateral cell membrane and transepithelial potentials following the addition of 10−5 M isoproterenol to the bath superfusate. Both responses were blocked by 10−6 M propranolol but neither response was mimicked by 10−4 M cAMP. β-Adrenergic binding studies of individual microdissected proximal tubules using (−)-[3H]CGP-12177 as a hydrophyllic radioligand and (±)-timolol (0.1 mM) as the displacer drug revealed two distinct populations of proximal tubules possessing either low (KD = 153.8 nM; Bmax = 110.2 fM/mm) or high affinity (KD = 12.0 nM; Bmax = 3.9 fM/mm) binding characteristics. Competition studies indicated that the bound (−)-[3H]CGP-12177 behaved as a typical β-adrenergic ligand, being displaced by (−)-isoproterenol but not by (+)-isoproterenol or (−)phenylephrine. However, neither appeared to be coupled to the adenylate cyclase system. These data suggest the presence of functional β-adrenergic receptors that do not appear to be coupled to the adenylate cyclase system.Key words: proximal tubule, β-receptors, adenylate cyclase.

Molecular Docking and Drug Discovery in β-Adrenergic Receptors

2017 ◽  
Vol 24 (39) ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Adrenergic Receptors ◽  
Β Adrenergic Receptors

scholarly journals Surgical treatment for common hepatic aneurysm. Original one-step technique

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 898-904
Author(s):  
Bruno Amato ◽  
Renato Patrone ◽  
Gennaro Quarto ◽  
Rita Compagna ◽  
Roberto Cirocchi ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Hepatic Artery ◽  
Distal Part ◽  
Intraoperative Ultrasound ◽  
Section Area ◽  
One Step ◽  
A New Technique ◽  
Open Surgical Treatment ◽  
The Right ◽  
Vascular Stapler

AbstractIntroductionHepatic artery aneurysms are rare, and their treatment represents a challenge for the surgeons.Materials and methodsA new technique is presented for common hepatic artery (CHA) aneurysm: it requires minimal vascular surgical dissection and only one linear vascular stapler is applied at the bottom of aneurysm. Aneurysm exclusion is easily obtained, which allowed retrograde thrombosis. Liver blood supply is ensured to the right and left hepatic artery, through the gastroduodenal artery, and can be previously monitored, with temporary clamping of the section area, by visual control, enzyme evaluation and intraoperative ultrasound examination. We reported an open surgical treatment, with simultaneous removal of hepatic and adrenal metastases, secondary to colon cancer.ResultsThe duration of vascular surgery was 30 min and did not involve complications. Postoperative controls confirmed the efficacy of the procedure.DiscussionThis original technique can be added to the various open and endovascular techniques so far described for the treatment of a CHA aneurysm. It is advisable as open surgery, mostly in case of associated pathologies.ConclusionsThe authors believe that this “one shot” technique by vascular staple of the distal part of CHA is minimally invasive and effective to obtain the exclusion of the aneurysm.

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