Beta-adrenoceptor regulation in the human heart: can it be monitored in circulating lymphocytes?
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.
Brodde
O E
OE
Biochemical Research Lab., University of Essen, F.R.G.
Michel
M C
MC
Gordon
E P
EP
Sandoval
A
A
Gilbert
E M
EM
Bristow
M R
MR
D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008991:Monitoring, Physiologic / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000097:blood* / Q000502:physiology
D011943:Receptors, Adrenergic, beta