title: Differential regulation of the β-adrenoceptor density and cyclic AMP level with age and sex in turkey cardiac chambers.
abstract: Decreased responses of the heart to β-adrenoceptor stimulation with aging have been shown to occur merely in selected heart chambers in relation to increased catecholamine levels. However, there are no systematic studies that investigate all cardiac chambers with regard to receptor density and cAMP (adenosine 3', 5'-cyclic monophosphate) responses. We used meat-type turkey poults (British United Turkey (B.U.T.) Big 6) with increasing age because their heart seems to decrease in weight in relation to body weight and they are often used as an animal model for heart failure. The receptor density and distribution were quantified by radioligand binding analysis using (-)-[(125)I]-iodocyanopindolol and β-adrenoceptor subtype-specific antagonists (ICI 118.551 and CGP 20712 A) in membranes of four cardiac chambers (right and left atria and ventricles) of 6-week-, 12-week-, 16/21-week-, and 57-week-old B.U.T. BIG 6 turkeys. Receptor function was determined by measuring basal and stimulated cAMP production. In both sexes, the β-adrenoceptor density decreased significantly in all chambers with age without altered β-adrenoceptor subtype distribution. The receptor affinity (KD) to the radioligand was similar in hearts of all age groups. β-adrenoceptor-(isoproterenol and guanosine 5'-triphosphate), G-protein-(NaF) and catalytic unit of adenylate cyclase (forskolin, Mn(2+)) mediated cAMP responses were not chamber-dependent. Indeed, the cAMP level was significantly lower in 57-week-old hearts than in 6-week-, 12-week-, 16/21-week-old hearts. These data suggest that with increasing age and body weight, the β-adrenoceptor signal transduction pathway was highly blunted in all cardiac chambers, occurring by decreased receptor density and cAMP responses.
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, d-04103 Leipzig, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Clinic for Birds and Reptiles, Faculty of Veterinary Medicine, University of Leipzig, d-04103 Leipzig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Böhme
authors.affiliation: Clinic for Birds and Reptiles, Faculty of Veterinary Medicine, University of Leipzig, d-04103 Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kube
authors.affiliation: GLU mbH, Rosa-Luxemburg-Damm 1, 15366 Neuenhagen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Haufe
authors.affiliation: Clinic for Birds and Reptiles, Faculty of Veterinary Medicine, University of Leipzig, d-04103 Leipzig, Germany.
authors.forename: Maria-Elisabeth
authors.initials: ME
authors.lastname: Krautwald-Junghanns
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, d-04103 Leipzig, Germany. Electronic address: gabraham@rz.uni-leipzig.de.
authors.forename: Getu
authors.initials: G
authors.lastname: Abraham
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009929:Organ Size; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012727:Sex Characteristics; D014422:Turkeys
chemical_list: D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases
keywords: Age; Cyclic AMP; Heart; Turkey; β-adrenoceptor