Direct labelling of myocardial β1-adrenoceptors

@article{Kaumann2004DirectLO,
  title={Direct labelling of myocardial $\beta$1-adrenoceptors},
  author={Alberto Julio Kaumann and Horst Lemoine},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={2004},
  volume={331},
  pages={27-39}
}
  • A. Kaumann, H. Lemoine
  • Published 2004
  • Biology, Medicine, Chemistry
  • Naunyn-Schmiedeberg's Archives of Pharmacology
SummaryA radioligand that selectively labels β1-adrenoceptors, 3H-(−)-bisoprolol (3H-BIS), is introduced. The binding properties of 3H-BIS to membrane particles of kitten heart are compared with the blocking properties of (−)-bisoprolol against stimulant effects of (−)-adrenaline and (−)-noradrenaline in heart preparations of kitten and guinea pig. 1.On kitten heart tissues (-)-bisoprolol antagonized the positive chronotropic and inotropic effects of catecholamines competitively. The effects… 
Direct labelling of β2-adrenoceptors
TLDR
The binding characteristics and non-linear regression analysis of blocking data with ICI 118,551 revelas that both β1- and β2-adrenoceptors contribute to the tracheo-relaxant and positive chronotropic effects of agonists.
The β2-adrenoceptor antagonist CGP 20712 A unmasks β2-adrenoceptors activated by (−)-adrenaline in rat sinoatrial node
  • A. Kaumann
  • Biology, Medicine
    Naunyn-Schmiedeberg's Archives of Pharmacology
  • 2004
TLDR
Results are consistent with an involvement in the rat of both β1-adrenoceptors (to a major extent) and β2-ad Renaline concentrations [only at high (−)-adrenaline concentrations] in the positive chronotropic effects of (−)- adrenaline.
β2-Adrenoceptor-mediated positive inotropic effect of adrenaline in human ventricular myocardium
TLDR
The contribution of β1- and β2-adrenoceptors to the positive inotropic effects of adrenaline and noradrenaline cannot be inferred straightforwardly from biochemical estimates of receptor fractions and fractional adenylate cyclase stimulation.
Relations between β-adrenoceptor occupancy and increases of contractile force and adenylate cyclase activity induced by catecholamines in human ventricular myocardium
TLDR
The more efficient activation of contractile force by (−)-noradrenaline in cat, compared to man, appears to be related to a 2-fold higher density of β1-adrenoceptors, a 6-foldHigher production of cyclic AMP per β1 -adrenOceptor and possibly to a more effective use of cyclIC AMP for contraction.
Regulation of ß-adrenoceptors in the guinea-pig sinoatrial node
TLDR
It is shown that changes in ß2-adrenoceptor density following 7 day (−)-isoprenaline infusion are compatible with reduced functional responsiveness in the SA node, and the reduction of al-adRenoceptor number in theSA node was also compatible with the reduced chronotropic response in this tissue.
Comparison of three radioligands for the labelling of human β-adrenoceptor subtypes
TLDR
All three radioligands are ill-suited to label β3-adrenoceptors, particularly in preparations co-expressing multiple subtypes, and in the absence of alternatives, [125I]-cyanopindolol appears the least unsuitable.
Some aspects of heart beta adrenoceptor function
  • A. Kaumann
  • Biology
    Cardiovascular Drugs and Therapy
  • 2009
TLDR
Both acute and chronic desensitization reduce positive inotropic responses to catecholamines, and chronic treatment of patients with β1AR-selective blockers paradoxically induces selective inotropic β2AR hyperreponsiveness.
Transdermal delivery of bupranolol: Pharmacodynamics and beta-adrenoceptor occupancy
TLDR
It is concluded that steady-state plasma concentrations and effect of the elsewise rapidly eliminated beta-blocker bupranolol can be achieved by a transdermal delivery system applied each day.
PET imaging of beta-adrenoceptors in human brain: a realistic goal or a mirage?
TLDR
Screening of more than 150 beta-blockers described in the literature yields only two compounds which can still be radiolabeled and evaluated for beta-adrenoceptor imaging and these radiopharmaceuticals showed a positive Ames test.
The role of cyclic AMP in the positive inotropic effect mediated by β1- and β2-adrenoceptors in isolated human right atrium
TLDR
It is concluded that cyclic AMP is involved in the positive inotropic action of isoprenaline evoked by β1- and β2-adrenoceptor stimulation in isolated human right atrium; however, an additional cyclicAMP independent mechanism cannot be ruled out.
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TLDR
The binding characteristics and non-linear regression analysis of blocking data with ICI 118,551 revelas that both β1- and β2-adrenoceptors contribute to the tracheo-relaxant and positive chronotropic effects of agonists.
An initial characterization of human heart β-adrenoceptors and their mediation of the positive inotropic effects of catecholamines
SummaryThe positive inotropic effects of catecholamines were studied on samples of ventricular myocardium taken from patients undergoing open heart surgery. The adenylyl cyclase and binding of
3H-(−)-Bupranolol, a new β-adrenoceptor radioligand: Characterization of its binding to kitten heart β-adrenoceptors
TLDR
It is concluded that 3H-BU is a useful tool for the study of myocardial β-adrenoceptors and all of the binding data are consistent with a model for a single class of non-interacting sites.
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TLDR
It is concluded that the concentration of physiological catecholamines at the human heart beta-adrenoceptors is limited by neuronal capture but not by extraneuronal uptake.
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TLDR
Detailed analysis of the competition curves displayed by the beta1 and beta2 selective drugs strongly suggest that beta1 or beta2 adrenoceptor binding sites coexist in different proportions within lung tissue in the two species.
Stimulant and blocking effects of optical isomers of pindolol on the sinoatrial node and trachea of guinea pig. Role of β-adrenoceptor subtypes in the dissociation between blockade and stimulation
TLDR
It is concluded that the positive chronotropic effects of (+)-pindolol are mediated predominantly by β2-adrenoceptors, although β1- adrenoceptor may also participate.
Potentiation of the effects of isoprenaline and noradrenaline by hydrocortisone in cat heart muscle
  • A. Kaumann
  • Biology, Medicine
    Naunyn-Schmiedeberg's Archives of Pharmacology
  • 2004
TLDR
Exposure of the tissues to 5 \gmM phenoxybenzamine resulted in an irreversible potentiation of the effects of (-)-isoprenaline and prevented the sensitizing action of hydrocortisone, presumably through a reversible blockade of some stage between the extraneuronal removal of catecholamines and their ultimate metabolism by COMT.
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TLDR
Some lipophilic antagonists which appear to be inert competitive ligands in fragmented membranes, alter receptor binding properties in intact cells, and seem to promote the transformation of receptor sites into a new “inactivated” state where competitive interactions between different ligands are inhibited.
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TLDR
In regard to ancillary pharmacological properties, ICI 118,551 has no partial agonist activity but has a membrane-stabilising action similar to that of propranolol, and the potency ratio for antagonism of vascular versus atrial actions of isoproterenol was greater than 250:1.
Heart ß-Receptors: On the Functional Role of Heterogeneous Binding Sites
TLDR
Receptor subtypes were studied in the myocardium of reserpine-pretreated kittens and binding of 3H-(−)-propranolol to membranes revealed saturable characteristics of a single class of complex.
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