title: Beta-adrenoceptor regulation in the human heart: can it be monitored in circulating lymphocytes?
abstract: In heart failure a decrease in cardiac beta-adrenoceptors presumably due to endogenous down-regulation by the elevated catecholamines is a general phenomenon. Thus, attempts have been made to assess beta-adrenoceptor function in patients with chronic heart failure in order to monitor the functional state of cardiac beta-adrenoceptors. The model most widely used is that of circulating lymphocytes that contain a homogeneous population of beta 2-adrenoceptors coupled to the adenylate cyclase/cyclic AMP system. The biochemical and pharmacological properties of beta 2-adrenoceptors present in lymphocytes are quite comparable to those of beta 2-adrenoceptors in the human heart, but clearly different from those of human cardiac beta 1-adrenoceptors. Furthermore, beta-adrenoceptor agonists and antagonists regulate lymphocyte beta 2- and cardiac beta 1- and beta 2-adrenoceptors in a subtype-selective fashion: while non-selective agonists (independent of exogenously applied or endogenously elevated) and antagonists affect both cardiac beta 1- and beta 2- as well as lymphocyte beta 2-adrenoceptors, beta 1-selective agonists and antagonists influence only cardiac beta 1-, but not cardiac and lymphocyte beta 2-adrenoceptors. Finally, direct comparison of lymphocyte and cardiac beta-adrenoceptor densities revealed that changes in lymphocyte beta 2-adrenoceptors are significantly correlated with changes in cardiac beta 2-adrenoceptors, but not related to changes in cardiac beta 1-adrenoceptors. Since beta 1-adrenoceptors predominate in all parts of the human heart, the use of lymphocyte beta 2-adrenoceptors as a tool for predicting the status of cardiac beta-adrenoceptors is, therefore, quite limited.
authors.affiliation: Biochemical Research Lab., University of Essen, F.R.G.
authors.forename: O E
authors.initials: OE
authors.lastname: Brodde
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
authors.forename: E P
authors.initials: EP
authors.lastname: Gordon
authors.forename: A
authors.initials: A
authors.lastname: Sandoval
authors.forename: E M
authors.initials: EM
authors.lastname: Gilbert
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
mesh_terms: D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008991:Monitoring, Physiologic / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000097:blood* / Q000502:physiology
chemical_list: D011943:Receptors, Adrenergic, beta