Differential regulation of the beta-adrenoceptor density and cyclic AMP level with age and sex in turkey cardiac chambers

作者：Hoffmann Sandra; Boehme Julia; Kube Christian; Haufe Joerg; Krautwald Junghanns Maria Elisabeth; Abraham Getu^*

来源：European Journal of Pharmacology, 2016, 777: 88-95.

DOI：10.1016/j.ejphar.2016.02.065

• Age
• beta-adrenoceptor
• Cyclic AMP
• Heart
• Turkey

Decreased responses of the heart to beta-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 (-)-[I-125]-iodocyanopindolol and beta-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 beta-adrenoceptor density decreased significantly in all chambers with age without altered beta-adrenoceptor subtype distribution. The receptor affinity (K-D) to the radioligand was similar in hearts of all age groups. beta-adrenoceptor-(isoproterenol and guanosine 5'-triphosphate), G-protein-(NaF) and catalytic unit of adenylate cyclase (forskolin, Mn2+ 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 beta-adrenoceptor signal transduction pathway was highly blunted in all cardiac chambers, occurring by decreased receptor density and cAMP responses.

• 出版日期2016-4-15