Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2-adrenoceptor
knockout mice. Obligatory role of beta1-adrenoceptors for putative
beta4-adrenoceptor pharmacology
A. Kaumann, S. Engelhardt, L. Hein, P. Molenaar, und M. Lohse. Naunyn Schmiedebergs Arch Pharmacol, 363 (1):
87-93(Januar 2001)Kaumann, A J Engelhardt, S Hein, L Molenaar, P Lohse, M Comparative
Study In Vitro Research Support, Non-U.S. Gov't Germany Naunyn-Schmiedeberg's
archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 2001
Jan;363(1):87-93..
Zusammenfassung
Some beta1- and beta2-adrenoceptor-blocking agents, such as (-)-CGP
12177, cause cardiostimulant effects at concentrations considerably
higher than those that antagonise the effects of catecholamines.
The cardiostimulant effects of these non-conventional partial agonists
are relatively resistant to blockade by (-)-propranolol and have
been proposed to be mediated through putative beta4-adrenoceptors
or through atypical states of either beta1- or beta2-adrenoceptors.
We investigated the effects of (-)-CGP 12177 on sinoatrial rate and
left atrial contractile force as well as the ventricular binding
of (-)-3HCGP 12177 in tissues from wild-type, beta2-adrenoceptor
knockout and beta1/beta2-adrenoceptor double knockout mice. The cardiostimulant
effects of (-)-CGP 12177 were present in wild-type and beta2-adrenoceptor
knockout mice but were absent in beta1/beta2-adrenoceptor double
knockout mice. Thus, the presence of beta1-adrenoceptors is obligatory
for the cardiostimulant effects of (-)-CGP 12177. It appears therefore
that an atypical state of the beta1-adrenoceptor contributes to the
mediation of the cardiostimulant effects induced by non-conventional
partial agonists. Ventricular beta1- and beta2-adrenoceptors, labelled
in wild-type with a K(D) approximately 0.5 nmol/l (approximately
16 fmol/mg protein), were absent in beta1/beta2-adrenoceptor double
knockout mice. However, a high density binding site (approximately
154-391 fmol/mg protein) that did not saturate completely (K(D) approximately
80-200 nM) was labelled by (-)-3HCGP 12177 in the three groups
of mice, being distinct from beta1- and beta2-adrenoceptors, as well
as from the site mediating the agonist effects of (-)-CGP 12177.
Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2-adrenoceptor
knockout mice. Obligatory role of beta1-adrenoceptors for putative
beta4-adrenoceptor pharmacology
Kaumann, A J Engelhardt, S Hein, L Molenaar, P Lohse, M Comparative
Study In Vitro Research Support, Non-U.S. Gov't Germany Naunyn-Schmiedeberg's
archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 2001
Jan;363(1):87-93.
%0 Journal Article
%1 Kaumann2001
%A Kaumann, A. J.
%A Engelhardt, S.
%A Hein, L.
%A Molenaar, P.
%A Lohse, M.
%D 2001
%J Naunyn Schmiedebergs Arch Pharmacol
%K & 1-Methyl-3-isobutylxanthine/pharmacology Adrenergic Animals Atria/*drug Atrial Binding, Bucladesine/pharmacology Competitive/drug Contraction/drug Dose-Response Drug Female Function Genotype Heart Isoproterenol/pharmacology Knockout Male Membranes/drug Mice Myocardial Node/drug Pindolol/*analogs Propanolamines/metabolism/*pharmacology Relationship, Sinoatrial Tritium/diagnostic beta-1/genetics/physiology beta-2/genetics/physiology beta-Agonists/pharmacology beta-Antagonists/*pharmacology beta/drug derivatives/pharmacology effects effects/metabolism effects/physiology use Receptor
%N 1
%P 87-93
%T Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2-adrenoceptor
knockout mice. Obligatory role of beta1-adrenoceptors for putative
beta4-adrenoceptor pharmacology
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11191841
%V 363
%X Some beta1- and beta2-adrenoceptor-blocking agents, such as (-)-CGP
12177, cause cardiostimulant effects at concentrations considerably
higher than those that antagonise the effects of catecholamines.
The cardiostimulant effects of these non-conventional partial agonists
are relatively resistant to blockade by (-)-propranolol and have
been proposed to be mediated through putative beta4-adrenoceptors
or through atypical states of either beta1- or beta2-adrenoceptors.
We investigated the effects of (-)-CGP 12177 on sinoatrial rate and
left atrial contractile force as well as the ventricular binding
of (-)-3HCGP 12177 in tissues from wild-type, beta2-adrenoceptor
knockout and beta1/beta2-adrenoceptor double knockout mice. The cardiostimulant
effects of (-)-CGP 12177 were present in wild-type and beta2-adrenoceptor
knockout mice but were absent in beta1/beta2-adrenoceptor double
knockout mice. Thus, the presence of beta1-adrenoceptors is obligatory
for the cardiostimulant effects of (-)-CGP 12177. It appears therefore
that an atypical state of the beta1-adrenoceptor contributes to the
mediation of the cardiostimulant effects induced by non-conventional
partial agonists. Ventricular beta1- and beta2-adrenoceptors, labelled
in wild-type with a K(D) approximately 0.5 nmol/l (approximately
16 fmol/mg protein), were absent in beta1/beta2-adrenoceptor double
knockout mice. However, a high density binding site (approximately
154-391 fmol/mg protein) that did not saturate completely (K(D) approximately
80-200 nM) was labelled by (-)-3HCGP 12177 in the three groups
of mice, being distinct from beta1- and beta2-adrenoceptors, as well
as from the site mediating the agonist effects of (-)-CGP 12177.
@article{Kaumann2001,
abstract = {Some beta1- and beta2-adrenoceptor-blocking agents, such as (-)-CGP
12177, cause cardiostimulant effects at concentrations considerably
higher than those that antagonise the effects of catecholamines.
The cardiostimulant effects of these non-conventional partial agonists
are relatively resistant to blockade by (-)-propranolol and have
been proposed to be mediated through putative beta4-adrenoceptors
or through atypical states of either beta1- or beta2-adrenoceptors.
We investigated the effects of (-)-CGP 12177 on sinoatrial rate and
left atrial contractile force as well as the ventricular binding
of (-)-[3H]CGP 12177 in tissues from wild-type, beta2-adrenoceptor
knockout and beta1/beta2-adrenoceptor double knockout mice. The cardiostimulant
effects of (-)-CGP 12177 were present in wild-type and beta2-adrenoceptor
knockout mice but were absent in beta1/beta2-adrenoceptor double
knockout mice. Thus, the presence of beta1-adrenoceptors is obligatory
for the cardiostimulant effects of (-)-CGP 12177. It appears therefore
that an atypical state of the beta1-adrenoceptor contributes to the
mediation of the cardiostimulant effects induced by non-conventional
partial agonists. Ventricular beta1- and beta2-adrenoceptors, labelled
in wild-type with a K(D) approximately 0.5 nmol/l (approximately
16 fmol/mg protein), were absent in beta1/beta2-adrenoceptor double
knockout mice. However, a high density binding site (approximately
154-391 fmol/mg protein) that did not saturate completely (K(D) approximately
80-200 nM) was labelled by (-)-[3H]CGP 12177 in the three groups
of mice, being distinct from beta1- and beta2-adrenoceptors, as well
as from the site mediating the agonist effects of (-)-CGP 12177.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Kaumann, A. J. and Engelhardt, S. and Hein, L. and Molenaar, P. and Lohse, M.},
biburl = {https://www.bibsonomy.org/bibtex/26c7a27279d99d3120dd03b830448ac6e/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {89c122c7ccd6a8d78d478a766bc78d25},
intrahash = {6c7a27279d99d3120dd03b830448ac6e},
issn = {0028-1298 (Print) 0028-1298 (Linking)},
journal = {Naunyn Schmiedebergs Arch Pharmacol},
keywords = {& 1-Methyl-3-isobutylxanthine/pharmacology Adrenergic Animals Atria/*drug Atrial Binding, Bucladesine/pharmacology Competitive/drug Contraction/drug Dose-Response Drug Female Function Genotype Heart Isoproterenol/pharmacology Knockout Male Membranes/drug Mice Myocardial Node/drug Pindolol/*analogs Propanolamines/metabolism/*pharmacology Relationship, Sinoatrial Tritium/diagnostic beta-1/genetics/physiology beta-2/genetics/physiology beta-Agonists/pharmacology beta-Antagonists/*pharmacology beta/drug derivatives/pharmacology effects effects/metabolism effects/physiology use Receptor},
month = Jan,
note = {Kaumann, A J Engelhardt, S Hein, L Molenaar, P Lohse, M Comparative
Study In Vitro Research Support, Non-U.S. Gov't Germany Naunyn-Schmiedeberg's
archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 2001
Jan;363(1):87-93.},
number = 1,
pages = {87-93},
shorttitle = {Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2-adrenoceptor
knockout mice. Obligatory role of beta1-adrenoceptors for putative
beta4-adrenoceptor pharmacology},
timestamp = {2010-12-14T18:22:40.000+0100},
title = {Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2-adrenoceptor
knockout mice. Obligatory role of beta1-adrenoceptors for putative
beta4-adrenoceptor pharmacology},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11191841},
volume = 363,
year = 2001
}