%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 }